Conversations With Peers About T2DM: Best Practices for Optimizing Treatment Using Weight Management as a Primary Goal
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About This Presentation
Chair, John E. Anderson, MD, discusses type 2 diabetes in this CME/NCPD/AAPA activity titled “Conversations With Peers About T2DM: Best Practices for Optimizing Treatment Using Weight Management as a Primary Goal.” For the full presentation, downloadable Practice Aids, and complete CME/NCPD/AAPA...
Slide Content
Conversations With Peers About T2DM
Best Practices for Optimizing Treatment Using
Weight Management as a Primary Goal
John E. Anderson, MD Javier Morales, MD, FACP, FACE
Past President Clinical Associate Professor of Medicine
The Frist Clinic Donald and Barbara Zucker School
Nashville, Tennessee of Medicine
Hofstra Northwell Hempstead
Vice President
Advanced Internal Medicine Group, PC
East Hills, New York
Go online to access full CME/NCPD/AAPA information, including faculty disclosures.
Best Practices for Optimizing Treatment Using
Weight Management as a Primary Goal
John E. Anderson, MD Javier Morales, MD, FACP, FACE
Past President Clinical Associate Professor of Medicine
The Frist Clinic Donald and Barbara Zucker School
Nashville, Tennessee of Medicine
Hofstra Northwell Hempstead
Vice President
Advanced Internal Medicine Group, PC
East Hills, New York
Go online to access full CME/NCPD/AAPA information, including faculty disclosures.
Disclosures
All relevant conflicts of interest have been mitigated prior to the commencement of
the activity.
Co-Chair/Planner
John E. Anderson, MD
Past President
The Frist Clinic
Nashville, Tennessee
John E. Anderson, MD, has a financial interest/relationship or affiliation in the form of:
Consultant and/or Advisor for Abbott; AstraZeneca; Bayer HealthCare Pharmaceuticals Inc.;
Boehringer Ingelheim Pharmaceuticals, Inc.; Lilly; Novo Nordisk Inc.; and Sanofi.
Speaker for Bayer HealthCare Pharmaceuticals Inc.; Lilly; Novo Nordisk Inc.; and Sanofi.
Copyright © 2001
24, PeerView
All relevant conflicts of interest have been mitigated prior to the commencement of
the activity.
Co-Chair/Planner
John E. Anderson, MD
Past President
The Frist Clinic
Nashville, Tennessee
John E. Anderson, MD, has a financial interest/relationship or affiliation in the form of:
Consultant and/or Advisor for Abbott; AstraZeneca; Bayer HealthCare Pharmaceuticals Inc.;
Boehringer Ingelheim Pharmaceuticals, Inc.; Lilly; Novo Nordisk Inc.; and Sanofi.
Speaker for Bayer HealthCare Pharmaceuticals Inc.; Lilly; Novo Nordisk Inc.; and Sanofi.
Copyright © 2001
24, PeerView
Disclosures
All relevant conflicts of interest have been mitigated prior to the commencement of
the activity.
Co-Chair/Planner Javier Morales, MD, FACP, FACE, has a
Javier Morales, MD, FACP, FACE financial interest/relationship or affiliation in the
Clinical Associate Professor of Medicine form of:
Donald and Barbara Zucker School
of Medicine
Hofstra Northwell Hempstead
Vice President
Advanced Internal Medicine Group, PC
East Hills, New York Speaker for Amgen Inc.; Bayer HealthCare
Pharmaceuticals Inc.; Boehringer Ingelheim
Pharmaceuticals, Inc.; Lilly; and Novo
Nordisk Inc.
Consultant and/or Advisor for Bayer
HealthCare Pharmaceuticals Inc.; Boehringer
Ingelheim Pharmaceuticals, Inc.; Lilly; and
Novo Nordisk Inc.
Copyright © 2000-2024, PeerView
All relevant conflicts of interest have been mitigated prior to the commencement of
the activity.
Co-Chair/Planner Javier Morales, MD, FACP, FACE, has a
Javier Morales, MD, FACP, FACE financial interest/relationship or affiliation in the
Clinical Associate Professor of Medicine form of:
Donald and Barbara Zucker School
of Medicine
Hofstra Northwell Hempstead
Vice President
Advanced Internal Medicine Group, PC
East Hills, New York Speaker for Amgen Inc.; Bayer HealthCare
Pharmaceuticals Inc.; Boehringer Ingelheim
Pharmaceuticals, Inc.; Lilly; and Novo
Nordisk Inc.
Consultant and/or Advisor for Bayer
HealthCare Pharmaceuticals Inc.; Boehringer
Ingelheim Pharmaceuticals, Inc.; Lilly; and
Novo Nordisk Inc.
Copyright © 2000-2024, PeerView
Planning Committee and Reviewer Disclosures
Planners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education,
do not have any relevant financial relationships related to this CE activity unless listed below.
Copyright © 2 24, PeerView
Planners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education,
do not have any relevant financial relationships related to this CE activity unless listed below.
Copyright © 2 24, PeerView
Our Goals for Today
Apply guidelines that prioritize weight loss as a treatment
target in PwT2DM
Overcome therapeutic inertia to intensify therapy in a timely
and appropriate manner when glycemic and weight goals
are unmet
Refine your shared decision-making skills to develop
individualized management plans to address glycemia
and weight
Copyright © 2001
Apply guidelines that prioritize weight loss as a treatment
target in PwT2DM
Overcome therapeutic inertia to intensify therapy in a timely
and appropriate manner when glycemic and weight goals
are unmet
Refine your shared decision-making skills to develop
individualized management plans to address glycemia
and weight
Copyright © 2001
Obesity, Hypertension, Dyslipidemia, and T2DM
Are Interrelated Diseases":
1 Vascular tone and
arterial stifness
e
=
Ei
Autonomic Lipid 3
Healthy ‘overactivity spilover en: 3
adipose » 4 aldosterone system E
tissue Highatdiets } El
Low physical activity 1 Liver
[102 Adipokine Anammation
‘Adipocyte hypertrophy Lis
‘and hyperplasia 7 oe
A x rate
Hypoxia inflammation 4
| Insulin 2
sensitivity
Most of the processes regulating these physiological y
3 ve | Muscle
functions are not under voluntary control perfusion
4. Saxton SN et a. Physiol Rev. 2019:99:1701.1783. 2. Miller TO etal Not Rev Drug Discov. 2022:21:201-228, 3. Yu YH etal. Obes Rev. 2015:16:234-247 PeerView.com
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Are Interrelated Diseases":
1 Vascular tone and
arterial stifness
e
=
Ei
Autonomic Lipid 3
Healthy ‘overactivity spilover en: 3
adipose » 4 aldosterone system E
tissue Highatdiets } El
Low physical activity 1 Liver
[102 Adipokine Anammation
‘Adipocyte hypertrophy Lis
‘and hyperplasia 7 oe
A x rate
Hypoxia inflammation 4
| Insulin 2
sensitivity
Most of the processes regulating these physiological y
3 ve | Muscle
functions are not under voluntary control perfusion
4. Saxton SN et a. Physiol Rev. 2019:99:1701.1783. 2. Miller TO etal Not Rev Drug Discov. 2022:21:201-228, 3. Yu YH etal. Obes Rev. 2015:16:234-247 PeerView.com
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ADA Standards: Holistic Person-Centered Approach
to T2DM Management!?
Ensure Strategies Are in Place to Detect
‘and Optimize Management of CV Risk Factors!
+ CV rik facto screoning and surveillance
+ BP lowering
+ Upid towering
+ Antkhrombal
moking coat
‘lycemie control needed, consider (
‘combination SGLTZUGLP-RA | \ a
+ General Kestyle + Intensivo, evidence
aduce. med based, structures
ston thar woightmanagmant
‘eating pater, program
wire aide + Consider motabotc
- Consider medication | surgery
for weight oss
‘The preferred pharmacothera
GLPS RA or dual
weight loss of
1. Davies MY et al. Diabetes Caro. PeerView.com
2. American Diabetes Associaton Professional Practice Commitoe, Diabetes Car, 2024;47(suppl 1) 5158-5178.
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
to T2DM Management!?
Ensure Strategies Are in Place to Detect
‘and Optimize Management of CV Risk Factors!
+ CV rik facto screoning and surveillance
+ BP lowering
+ Upid towering
+ Antkhrombal
moking coat
‘lycemie control needed, consider (
‘combination SGLTZUGLP-RA | \ a
+ General Kestyle + Intensivo, evidence
aduce. med based, structures
ston thar woightmanagmant
‘eating pater, program
wire aide + Consider motabotc
- Consider medication | surgery
for weight oss
‘The preferred pharmacothera
GLPS RA or dual
weight loss of
1. Davies MY et al. Diabetes Caro. PeerView.com
2. American Diabetes Associaton Professional Practice Commitoe, Diabetes Car, 2024;47(suppl 1) 5158-5178.
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
ADA Standards: Prioritization of Glucose-Lowering
Therapies to Meet Different Individualized Goals!
Reduce ASCVD Risk Reduce A1C
Choose approaches that provide the
efficacy to achieve goals
Metformin OR agent(s) including
COMBINATION therapy; prioritize
GLP-1 RA with proven
CVD benefit
+ Dulaglutide
+ Liraglutide
+ Semaglutide injection
Dulaglutide (high dose),
somaglutide, tizepatide, insulin,
‘combination oral, combination
Injectable (GLP-1 RAVInsulin)
GLP-1 RA (not listed above),
metformin, SGLT2i, sulfonylurea,
Alternative treatment
strategies
+ SGLT2i with proven CVD benefit
+ GLP-1 RA + SGLT2i
+ GLP-1 RA or SGLT2i + TZD
DPP-4i
Reduce Weight
The preferred pharmacotherapy
should be a GLP-1 RA or dual
GIPIGLP-1 RA with greater weight
loss efficacy
Very High Somaglutido, tirzopatide
High Dulaglutide, liraglutide
Intermediate
GLP-1 RA (not covered above),
SGLTA
Neutral DPP-4i metformin
Consult ADA guidelines for treatment recommendations if HF or CKD goals are prioritized
1. American Diabetes Associaton Professional Practice Commätoo. Diabetos Caro. 2024;47(suppl 1) 158-8178.
PeerView.com/USQ827
PeerView.com
Copyright © 2000-2024, PeerView
Therapies to Meet Different Individualized Goals!
Reduce ASCVD Risk Reduce A1C
Choose approaches that provide the
efficacy to achieve goals
Metformin OR agent(s) including
COMBINATION therapy; prioritize
GLP-1 RA with proven
CVD benefit
+ Dulaglutide
+ Liraglutide
+ Semaglutide injection
Dulaglutide (high dose),
somaglutide, tizepatide, insulin,
‘combination oral, combination
Injectable (GLP-1 RAVInsulin)
GLP-1 RA (not listed above),
metformin, SGLT2i, sulfonylurea,
Alternative treatment
strategies
+ SGLT2i with proven CVD benefit
+ GLP-1 RA + SGLT2i
+ GLP-1 RA or SGLT2i + TZD
DPP-4i
Reduce Weight
The preferred pharmacotherapy
should be a GLP-1 RA or dual
GIPIGLP-1 RA with greater weight
loss efficacy
Very High Somaglutido, tirzopatide
High Dulaglutide, liraglutide
Intermediate
GLP-1 RA (not covered above),
SGLTA
Neutral DPP-4i metformin
Consult ADA guidelines for treatment recommendations if HF or CKD goals are prioritized
1. American Diabetes Associaton Professional Practice Commätoo. Diabetos Caro. 2024;47(suppl 1) 158-8178.
PeerView.com/USQ827
PeerView.com
Copyright © 2000-2024, PeerView
Early Glycemic Control Matters!
Microvascular Macrovascular Mortality
> — Pos
3 «| — 5
E - +
é «4 =
g A +
5 « o
E |
2 04 -7 =
a a - -
E «| Le
5
a - AS
“ si 5 nn an
Adjusted Hazard Ratio
© AIC 6.5% to <7.0% (48 to <53 mmolmol) 4 AIC 8.0% to <9.0% (64 to <75 mmol/mol)
M A1C 7.0% to <8.0% (53 to <64 mmol/mol) $ AIC 9.0% (>75 mmolimol)
1. Lateerapong Net a. botas Gare. 2019:42416-425 PeerView.com
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
Microvascular Macrovascular Mortality
> — Pos
3 «| — 5
E - +
é «4 =
g A +
5 « o
E |
2 04 -7 =
a a - -
E «| Le
5
a - AS
“ si 5 nn an
Adjusted Hazard Ratio
© AIC 6.5% to <7.0% (48 to <53 mmolmol) 4 AIC 8.0% to <9.0% (64 to <75 mmol/mol)
M A1C 7.0% to <8.0% (53 to <64 mmol/mol) $ AIC 9.0% (>75 mmolimol)
1. Lateerapong Net a. botas Gare. 2019:42416-425 PeerView.com
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
Lifetime Risk of CVD Morbidity and Mortality
Among Middle-Aged Individuals’
Middle-Aged Men Middle-Aged Women
Severely obese
Severely obese chose
‘Underweight
8858838388
Lifetime Risk of CVD
Morbidity and Mortality, %
5 0 E mS Sw 0 5 D 2 % D % 4 4 © 5 m
Follow-Up, y Follow-Up, y
+ Lifetime risks for total cardiovascular disease exceeded 30% for men and women in all BMI groups!
+ Participants in higher BMI strata had higher lifetime risks for cardiovascular disease through age 95 years!
+ However, all-cause mortality is higher for underweight individuals?
+ Population-based st usa poled indidusovel data rom acute across 10 arg US prospective cohorts, 3.2 millon prson years of ala. rom 1964102015
Data shown present raining cumulative Heime sk estimates total CVD evens adjusts for competing ek of nancarovakeular Seth) In mele-aged (nex
ge. 40.9 yes) men and women sed by EMI groups undermagh. perme. Overwegi. Obese. and severely obese. fs
1.Khan 88 et a. JAMA Corde 2018:3280-287. 2. Bhaskaran Ket a. Lanco Diabetes Endocrinol. 20186 344-95. PeerView.com
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
Among Middle-Aged Individuals’
Middle-Aged Men Middle-Aged Women
Severely obese
Severely obese chose
‘Underweight
8858838388
Lifetime Risk of CVD
Morbidity and Mortality, %
5 0 E mS Sw 0 5 D 2 % D % 4 4 © 5 m
Follow-Up, y Follow-Up, y
+ Lifetime risks for total cardiovascular disease exceeded 30% for men and women in all BMI groups!
+ Participants in higher BMI strata had higher lifetime risks for cardiovascular disease through age 95 years!
+ However, all-cause mortality is higher for underweight individuals?
+ Population-based st usa poled indidusovel data rom acute across 10 arg US prospective cohorts, 3.2 millon prson years of ala. rom 1964102015
Data shown present raining cumulative Heime sk estimates total CVD evens adjusts for competing ek of nancarovakeular Seth) In mele-aged (nex
ge. 40.9 yes) men and women sed by EMI groups undermagh. perme. Overwegi. Obese. and severely obese. fs
1.Khan 88 et a. JAMA Corde 2018:3280-287. 2. Bhaskaran Ket a. Lanco Diabetes Endocrinol. 20186 344-95. PeerView.com
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
Few Individuals With T2DM Have Optimal Cardiovascular
Risk Control: NHANES, 2013-20161
84 84 86
“0
73 nonsmoker
Ss”
Bo} 6 56 57
© 51
© à 50 50 49
+
ù
HA 2
En»
10 9 10 ;
| Em
AIC Blood Pressure LDL-C Smoking Status BMI BMI
Goals: <7%, no CVD <130/80 mmHg <100 mg/dL, no CVD Non-smoking <30 kim? <25 kg/m?
<8%, CVD <70 mg/dL, CVD
Individual Risk Factors at Goal
1 Andary R et al. Am J Canto. 2019,124:522:521. PeerView.com
PeerView.com/USQ827
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Risk Control: NHANES, 2013-20161
84 84 86
“0
73 nonsmoker
Ss”
Bo} 6 56 57
© 51
© à 50 50 49
+
ù
HA 2
En»
10 9 10 ;
| Em
AIC Blood Pressure LDL-C Smoking Status BMI BMI
Goals: <7%, no CVD <130/80 mmHg <100 mg/dL, no CVD Non-smoking <30 kim? <25 kg/m?
<8%, CVD <70 mg/dL, CVD
Individual Risk Factors at Goal
1 Andary R et al. Am J Canto. 2019,124:522:521. PeerView.com
PeerView.com/USQ827
Copyright © 2000-2024, PeerView
Overcoming Therapeutic Inertia in T2DM:
Clinician/Practice-Level Interventions!
Understand Impact
of Treatment Inertia
+ Schedule “diabetes only” visits
where you and your patients can
focus solely on diabetes
Ask office staff to remind patients
to bring their glucose logs, list of
medications, and monitoring
devices
Aim to adjust therapy any time a
patients A1C or other targets are
not at goal
Consider making changes
between A1C tests based on
monitoring results
1. hips lew therapeutcinerta diabetes oglaboutherapeute ini.
PeerView.com/USQ827
Recognize
Treatment Inertia
+ Check for barriers
— Diabetes distress
- Depression
— Low health literacy
— Social determinants of health
Schedule follow-ups based on A1C
~ Every 6-8 weeks for those at
9% or higher
— Every 2-3 months for those at
7% to 8.9%
— Every 3-6 months for those less
than 7% or at their personal target
Plan With
Patients
+ Develop a diabetes care plan
that includes a personal
AIC target
+ Take into account patient
needs, concerns, and wishes
+ Review and update regularly
+ Refer all patients for diabetes
self-management education
when diagnosed or if they
have not been before
PeerView.com
Copyright © 2000-2024, PeerView
Clinician/Practice-Level Interventions!
Understand Impact
of Treatment Inertia
+ Schedule “diabetes only” visits
where you and your patients can
focus solely on diabetes
Ask office staff to remind patients
to bring their glucose logs, list of
medications, and monitoring
devices
Aim to adjust therapy any time a
patients A1C or other targets are
not at goal
Consider making changes
between A1C tests based on
monitoring results
1. hips lew therapeutcinerta diabetes oglaboutherapeute ini.
PeerView.com/USQ827
Recognize
Treatment Inertia
+ Check for barriers
— Diabetes distress
- Depression
— Low health literacy
— Social determinants of health
Schedule follow-ups based on A1C
~ Every 6-8 weeks for those at
9% or higher
— Every 2-3 months for those at
7% to 8.9%
— Every 3-6 months for those less
than 7% or at their personal target
Plan With
Patients
+ Develop a diabetes care plan
that includes a personal
AIC target
+ Take into account patient
needs, concerns, and wishes
+ Review and update regularly
+ Refer all patients for diabetes
self-management education
when diagnosed or if they
have not been before
PeerView.com
Copyright © 2000-2024, PeerView
How Much Weight Loss Is Needed to Improve Health?
+ Notas much as many patients would like
Improves to lose!
healtht> —
- Unrealistic weight loss goals are common and
self-defeatingi0-13
Reverses some + Weight loss of 5% to 10% may be disappointing
disease to patients’
prosas — Itis better to set a 5% goal and celebrate that
success than to set a 20% goal with inadequate
Reduces CV resources and quit in frustration
events and
complications?
1. Wing RR et al Disbatos Coro. 2011:34:1481-1486, 2. Lazo M ot a. Dinbotos Core. 2010:39:2156-2163. 3.
4. Wing RR et a. Diabotes Coro. 2019.96:2037.2044. 5, Ming RR et al. Sox Mod. 2010.7:156-165. 6 Engel
7. PronvatK et al Hepatology. 2010.51:121-129. 8. Foster GD
10. Pere B tal. Prov Mod Rop. 2018,12:12-19. 11. van Rijswijk AS et al. Surg Obos Rolat Dis, 2021:17:130-146, PeerView.
12. Concoigao EM el al Surg Obes Rolo Dis 2020,16:952.956. 13. Black Cet al Psychol Heath, 2071.36 994-851 eerView.com
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
+ Notas much as many patients would like
Improves to lose!
healtht> —
- Unrealistic weight loss goals are common and
self-defeatingi0-13
Reverses some + Weight loss of 5% to 10% may be disappointing
disease to patients’
prosas — Itis better to set a 5% goal and celebrate that
success than to set a 20% goal with inadequate
Reduces CV resources and quit in frustration
events and
complications?
1. Wing RR et al Disbatos Coro. 2011:34:1481-1486, 2. Lazo M ot a. Dinbotos Core. 2010:39:2156-2163. 3.
4. Wing RR et a. Diabotes Coro. 2019.96:2037.2044. 5, Ming RR et al. Sox Mod. 2010.7:156-165. 6 Engel
7. PronvatK et al Hepatology. 2010.51:121-129. 8. Foster GD
10. Pere B tal. Prov Mod Rop. 2018,12:12-19. 11. van Rijswijk AS et al. Surg Obos Rolat Dis, 2021:17:130-146, PeerView.
12. Concoigao EM el al Surg Obes Rolo Dis 2020,16:952.956. 13. Black Cet al Psychol Heath, 2071.36 994-851 eerView.com
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
Comparative Efficacy: Differential Effects of Various
Glucose-Lowering Agents for T2DM'
AIC, % Change in Body Weight, kg Hypoglycemia <70 mg/dL
‘Comparison: Other Comparison: Other
Placebo (Random vs Placebo (Random MD (25% Cl) vs Placebo (Random MD (95% CI)
Effects Model) Effects Model) Effects Model)
Tizepatde 15 ma 2.00 (22210-1.78) Trzepatie 18 mg. EI 10.08 (1045 10-072) Semaguido 2 mg 1049 (0.17 to 126)
Trzopatdo 10 mg 1.8 (209 0 1.63) Tirzopatide 10 mg 827 (2661-788) soLrz ces 1010410)
Tizepatdo 4 mg 1.63 (2.0910 1.30) SGLTZ + GLP-1 RA $47 (6.1610-479) GLP. RA (066 (0320 137)
Beal insuin + SU “1.82 (236 10-088) Tirepatido 5 mq 545 (58510-506) Tizepaige 5 mg 132 (0740237)
¡DegLia 1.901.880 1.39) Dulogutide 4.5 mg, 361 (408t0-315). y, 103510:
Bscalbols nsula “1.80 (222 10-08) Somagiutde 2 mg 353 (4.36 0.2.70) Trio 10m9 en
¡ciar 52 (1.8210 1.22) SGLT2: 344 (4.11 t0-2.77)) Tizeatide 1579 TEEN
SGLT2i+GLP-1 RA 131 (1.7110-0.91) Dulagluido 3 mg 3.16 (3.62 to-2.69) SOLT2+ GLPARA ed
BlAsp30 3) GLP-1 RA 2.63 (2.96 to-2.29) Er i à en
Semagutiée 2 mg, 50) ¡Glas 005 (037 to 046) nul + ot
Dulaghtide 4.5 mg. 0.70) Deglira 010034054) Dulaghtide 4.5 mg He 329 (0.67 10 16.18)
Dutaghtie 3 mg 00 (1.41 to-0.59) Basal insu 152(1.1310 191) IDoglia 479 (1.85t0 1241)
Bosal insulin 090 (1181-088) Basal insulin + SU, 165(0.0210327) Basa insuin 527 (28210982)
SLP RA 0.89 (1.19 10-0.64) BIAsp30 195 (11010 270) (Glen 547 (28010 1068)
SOLTA 046 (02610006) Basolbolusinsulo, M 360126610454) | Binspao fe 997 049102250)
This meta-analysis of forty trials concludes with the following hierarchy of treatment options:
rzepatide, then GLP-1 RA + basal insulin FRC, then GLP-1 RA + SGLT2i
1. Caruso |e al. eCincalMechche. 2024/64: 102181 PeerView.com
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
Glucose-Lowering Agents for T2DM'
AIC, % Change in Body Weight, kg Hypoglycemia <70 mg/dL
‘Comparison: Other Comparison: Other
Placebo (Random vs Placebo (Random MD (25% Cl) vs Placebo (Random MD (95% CI)
Effects Model) Effects Model) Effects Model)
Tizepatde 15 ma 2.00 (22210-1.78) Trzepatie 18 mg. EI 10.08 (1045 10-072) Semaguido 2 mg 1049 (0.17 to 126)
Trzopatdo 10 mg 1.8 (209 0 1.63) Tirzopatide 10 mg 827 (2661-788) soLrz ces 1010410)
Tizepatdo 4 mg 1.63 (2.0910 1.30) SGLTZ + GLP-1 RA $47 (6.1610-479) GLP. RA (066 (0320 137)
Beal insuin + SU “1.82 (236 10-088) Tirepatido 5 mq 545 (58510-506) Tizepaige 5 mg 132 (0740237)
¡DegLia 1.901.880 1.39) Dulogutide 4.5 mg, 361 (408t0-315). y, 103510:
Bscalbols nsula “1.80 (222 10-08) Somagiutde 2 mg 353 (4.36 0.2.70) Trio 10m9 en
¡ciar 52 (1.8210 1.22) SGLT2: 344 (4.11 t0-2.77)) Tizeatide 1579 TEEN
SGLT2i+GLP-1 RA 131 (1.7110-0.91) Dulagluido 3 mg 3.16 (3.62 to-2.69) SOLT2+ GLPARA ed
BlAsp30 3) GLP-1 RA 2.63 (2.96 to-2.29) Er i à en
Semagutiée 2 mg, 50) ¡Glas 005 (037 to 046) nul + ot
Dulaghtide 4.5 mg. 0.70) Deglira 010034054) Dulaghtide 4.5 mg He 329 (0.67 10 16.18)
Dutaghtie 3 mg 00 (1.41 to-0.59) Basal insu 152(1.1310 191) IDoglia 479 (1.85t0 1241)
Bosal insulin 090 (1181-088) Basal insulin + SU, 165(0.0210327) Basa insuin 527 (28210982)
SLP RA 0.89 (1.19 10-0.64) BIAsp30 195 (11010 270) (Glen 547 (28010 1068)
SOLTA 046 (02610006) Basolbolusinsulo, M 360126610454) | Binspao fe 997 049102250)
This meta-analysis of forty trials concludes with the following hierarchy of treatment options:
rzepatide, then GLP-1 RA + basal insulin FRC, then GLP-1 RA + SGLT2i
1. Caruso |e al. eCincalMechche. 2024/64: 102181 PeerView.com
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
GLP-1 RAs and GIP/GLP-1 RAs at High Doses in PwT2DM:
A1C and Weight Reductions From Baseline!”.a
A1C
y
1.0% to <1.5%
DULA 1.5 mg QW
EXN 2 mg QW
LIRA 1.8 mg QD
LIXI 20 meg QD
SEMA 14 mg PO QD
AIC |
0.4% to <1.0%
EXN 10 mcg BID
LIX! 20 meg QD
SEMA 14 mg PO QD
Weight |
0 kg to <5 kg
A1C
1 AIC |
1.5% to <2.0%
2.0% to 2.5%
DULA 3 mg QW
DULA 4.5 mg QW
LIRA 1.8 mg QD
Weight |
5 kg to <10 kg
Weight |
10 kg to 15 kg
LP: Rar CPI RA acto con. ome ele esimande fr ls str 24-48
omita Ba
SEMA 1 mg QW
SEMA 2 mg QW | SEMA 2 mg QW
SEMA 2.4 mg QW
TZP 10 mg QW
= TZP 15 mg QW
goal ens: at shown ae
Batts ir 200 ay ia Fo nd DAS EE lo Pu Das Crm aaa res
Pen es Endocrine
À Obweat te Lo ator sor ante
PeerView.com/USQ827
0218874. 5. Frias JP at a NEng Med 2021385 5085156, Ll Bo al Lance 202108 89-508,
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A1C and Weight Reductions From Baseline!”.a
A1C
y
1.0% to <1.5%
DULA 1.5 mg QW
EXN 2 mg QW
LIRA 1.8 mg QD
LIXI 20 meg QD
SEMA 14 mg PO QD
AIC |
0.4% to <1.0%
EXN 10 mcg BID
LIX! 20 meg QD
SEMA 14 mg PO QD
Weight |
0 kg to <5 kg
A1C
1 AIC |
1.5% to <2.0%
2.0% to 2.5%
DULA 3 mg QW
DULA 4.5 mg QW
LIRA 1.8 mg QD
Weight |
5 kg to <10 kg
Weight |
10 kg to 15 kg
LP: Rar CPI RA acto con. ome ele esimande fr ls str 24-48
omita Ba
SEMA 1 mg QW
SEMA 2 mg QW | SEMA 2 mg QW
SEMA 2.4 mg QW
TZP 10 mg QW
= TZP 15 mg QW
goal ens: at shown ae
Batts ir 200 ay ia Fo nd DAS EE lo Pu Das Crm aaa res
Pen es Endocrine
À Obweat te Lo ator sor ante
PeerView.com/USQ827
0218874. 5. Frias JP at a NEng Med 2021385 5085156, Ll Bo al Lance 202108 89-508,
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Motivating Patients With
Individualized Management
and Shared Decision-Making
Individualized Management
and Shared Decision-Making
Case Introduction:
Simon Kowalski, a Man Aged 47 Years
BMI: 31.9 kg/m?; height: 71 inches (180 cm); Patient Notes
weight 229 Ib (104 kg) + Electrician from Staten Island, NY
A1C: 6.9%; BP: 136/82 mmHg » Divorced with two adult children (one is married
Medical history: obesity, hypertension, T2DM (5 y), and the otherin colege)
each + Ex-wife used to tell him his snoring was “very bad"
- Gradually increasing weight, glycemia, and BP Visit Notes
in the last 3 y + Today's telehealth appointment is for a lower
Ree back pain flare up due to musculoskeletal injury
Current medications while working
— Metformin 1,000 mg/sitagliptin 100 mg + Began a discussion about his weight; claims he gets
combination tablet, once daily exercise on the job; fast food for most meals.
- Losartan 50 mg, once daily + Suggested change in T2DM meds; patient declines
Proseribed today terinjuny and says to bring it up at next appointment
- Muscle relaxant/anti-inflammatory
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Simon Kowalski, a Man Aged 47 Years
BMI: 31.9 kg/m?; height: 71 inches (180 cm); Patient Notes
weight 229 Ib (104 kg) + Electrician from Staten Island, NY
A1C: 6.9%; BP: 136/82 mmHg » Divorced with two adult children (one is married
Medical history: obesity, hypertension, T2DM (5 y), and the otherin colege)
each + Ex-wife used to tell him his snoring was “very bad"
- Gradually increasing weight, glycemia, and BP Visit Notes
in the last 3 y + Today's telehealth appointment is for a lower
Ree back pain flare up due to musculoskeletal injury
Current medications while working
— Metformin 1,000 mg/sitagliptin 100 mg + Began a discussion about his weight; claims he gets
combination tablet, once daily exercise on the job; fast food for most meals.
- Losartan 50 mg, once daily + Suggested change in T2DM meds; patient declines
Proseribed today terinjuny and says to bring it up at next appointment
- Muscle relaxant/anti-inflammatory
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Overweight and Obesity Increases the Risk of Back Injuries:
Evidence From the US Navy and Marines!
Unadjusted Prevalence Ratios for Musculoskeletal Back Injuries by
BMI Categories 2009-2015 (N = 424,460-437,053)
_ m Overweight vs healthy
=, m Obese vs healthy
ao
>
=
=
3
12
Y
ES
2
5
ey
3
3
$
8
E
$ 0
à 2011 2013 2014
1: Malinax RA et al. Mi Mod, 2023;188 61094-01101 PeerView.com
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
Evidence From the US Navy and Marines!
Unadjusted Prevalence Ratios for Musculoskeletal Back Injuries by
BMI Categories 2009-2015 (N = 424,460-437,053)
_ m Overweight vs healthy
=, m Obese vs healthy
ao
>
=
=
3
12
Y
ES
2
5
ey
3
3
$
8
E
$ 0
à 2011 2013 2014
1: Malinax RA et al. Mi Mod, 2023;188 61094-01101 PeerView.com
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
Communicating Within the Patient Encounter!
Is now a good time for us to discuss how your weight and health may be affecting each other
and how we can work together on i
m Yes
Questions to Ask the Patient
+ What concerns you most about your weight? E ee Fo =
+ What is the most important outcome you hope to achieve with weight loss? acaso
+ What would stand in the way of achieving that outcome? am concemed about the impact of
+ Is there a first step that you are ready to take? your weight on your health. There
may be some things we can do
+ What impact will the changes we have discussed have on your life? A
. E N together in the fulure. Please make
se Eis problem; what frequency and type of follow-up would een
de are ready for another discussion.”
Response From PCP
+ Acknowledge concems + Provide resources
+ Link obesity to comorbidities + Schedule follow-up or referral
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Is now a good time for us to discuss how your weight and health may be affecting each other
and how we can work together on i
m Yes
Questions to Ask the Patient
+ What concerns you most about your weight? E ee Fo =
+ What is the most important outcome you hope to achieve with weight loss? acaso
+ What would stand in the way of achieving that outcome? am concemed about the impact of
+ Is there a first step that you are ready to take? your weight on your health. There
may be some things we can do
+ What impact will the changes we have discussed have on your life? A
. E N together in the fulure. Please make
se Eis problem; what frequency and type of follow-up would een
de are ready for another discussion.”
Response From PCP
+ Acknowledge concems + Provide resources
+ Link obesity to comorbidities + Schedule follow-up or referral
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4. ps stop publenoatth gu 0du/Rosources
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Stigmatization About T2DM and Weight Is Entrenched
in US Healthcare Practice!»
Attitudes of Physicians Toward Patients
88
80
72 ro ee
64
ss 87
47
40
20
o
Personally responsible for Patient's own fault they Some have no willpower Could lose some weight
their disease have this disease with a little exercise
=T2DM mObesity
Physicians, %
Survey of 205 physicians from a rationaly representative panel, January 2023,
10827.
‘Bonnett BL Puh RN. Babes Res Cin Pac! 2023202108 PeerView.com
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
in US Healthcare Practice!»
Attitudes of Physicians Toward Patients
88
80
72 ro ee
64
ss 87
47
40
20
o
Personally responsible for Patient's own fault they Some have no willpower Could lose some weight
their disease have this disease with a little exercise
=T2DM mObesity
Physicians, %
Survey of 205 physicians from a rationaly representative panel, January 2023,
10827.
‘Bonnett BL Puh RN. Babes Res Cin Pac! 2023202108 PeerView.com
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
Life’s Essential 8: Healthy Living Is for Everyone
American Heart Association Guidelines?
ES Eat better Manage cholesterol
O .
ia Be more active Manage blood pressure
© Quit tobacco Manage blood sugar
Gy Get healthy sleep Bl Manage weight
A. ps unn hearLorg/-imodiaHealty-Living Fils/LES-Fact Sheetsi.ites_ Essential 8 Fact Shoot pol. 2. LIoyc-Jones OM etal Caculaton. 2022146018... PeerView.com
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American Heart Association Guidelines?
ES Eat better Manage cholesterol
O .
ia Be more active Manage blood pressure
© Quit tobacco Manage blood sugar
Gy Get healthy sleep Bl Manage weight
A. ps unn hearLorg/-imodiaHealty-Living Fils/LES-Fact Sheetsi.ites_ Essential 8 Fact Shoot pol. 2. LIoyc-Jones OM etal Caculaton. 2022146018... PeerView.com
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Duration of Overweight/Obesity and
Degree of Activity Matters12>
CVD Risk Increases With Longer Duration + Negative legacy effect
of Overweight and Inactivity with respect to the
20 . es duration of overweight
= Mpio Bi Inactive and physical activity
14 1.25
+ Overweight with
CVD Risk Score (range: 0-6)
12 1.00 aie
10 CES inactivity leads to worse
9 outcomes than
= 0.43 ; A a
0% overweight with activity
9) 5 NIA
Healthy weight now Overweight now Overweight now
and 10 y ago but not 10 y ago and 10 y ago
2 1,443 asus agnd 96-05 years, NHANES 2009-2006. CVD risk cor ranged fom 0: ases onto total numa of CVD rik factor: (1) hypertension
{2140180 mo) (2) labels (lasting lucose 2126 mg. or ATC 26.3%) (hgh vod ca stun with (°14 6%) (2) gh CRP (203 mL} 5) ow HOL
{male 40 moi. female <80 mp () hgh TG (180 mL ñ
1. Dankel SJ etai. tJ Candol.2015201.P38-P89, PeerView.com
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
Degree of Activity Matters12>
CVD Risk Increases With Longer Duration + Negative legacy effect
of Overweight and Inactivity with respect to the
20 . es duration of overweight
= Mpio Bi Inactive and physical activity
14 1.25
+ Overweight with
CVD Risk Score (range: 0-6)
12 1.00 aie
10 CES inactivity leads to worse
9 outcomes than
= 0.43 ; A a
0% overweight with activity
9) 5 NIA
Healthy weight now Overweight now Overweight now
and 10 y ago but not 10 y ago and 10 y ago
2 1,443 asus agnd 96-05 years, NHANES 2009-2006. CVD risk cor ranged fom 0: ases onto total numa of CVD rik factor: (1) hypertension
{2140180 mo) (2) labels (lasting lucose 2126 mg. or ATC 26.3%) (hgh vod ca stun with (°14 6%) (2) gh CRP (203 mL} 5) ow HOL
{male 40 moi. female <80 mp () hgh TG (180 mL ñ
1. Dankel SJ etai. tJ Candol.2015201.P38-P89, PeerView.com
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
The Effects of Weight Loss on CV Risk Factors in PwT2DM:
Lessons Learned from Look AHEAD!
Change in A1C % Change in Blood Pressure Change in HDL and LDL
by Weight Loss Category by Weight Loss Category by Weight Loss Category
5 .
02 | | 2” | yes 1
Es ? 1
z A a.) pif
gos E Bo E peo 2 HDL: P<.0001
E em E E ey mers
5 E 3
© oo ye Eu
5 B B
8 $ 8 +
ail = aS ee ee ae ENT
Ho 6 38
Gain Zr - - -
1. Wing RR et al. Diobotos Caro. 2011:34:1481-1486.
PeerView.com/USQ827
= m 46
215
LS ur - - -
= m ‘48
Gain, zur -
PeerView.com
Copyright © 2000-2024, PeerView
Lessons Learned from Look AHEAD!
Change in A1C % Change in Blood Pressure Change in HDL and LDL
by Weight Loss Category by Weight Loss Category by Weight Loss Category
5 .
02 | | 2” | yes 1
Es ? 1
z A a.) pif
gos E Bo E peo 2 HDL: P<.0001
E em E E ey mers
5 E 3
© oo ye Eu
5 B B
8 $ 8 +
ail = aS ee ee ae ENT
Ho 6 38
Gain Zr - - -
1. Wing RR et al. Diobotos Caro. 2011:34:1481-1486.
PeerView.com/USQ827
= m 46
215
LS ur - - -
= m ‘48
Gain, zur -
PeerView.com
Copyright © 2000-2024, PeerView
What Advice Can We Give Our Patients About
Lifestyle Modifications?1+4
“Lifestyle modifications” mea
Look AHEAD study A practical starting point
Referral to diabetes
fferent things in different contexts
Frequent, educator or clinical
aes 5 multidisciplinary Walking 175 or nutritionist
Significant time ; À
eb em counseling and more minutes (Physician referral/
follow-up per week endorsement is the
appointments strongest predictor that
a patient will go!)
1. Look AHEAD Research Group at al. Obesty (Siver Spring). 2006:14:737-752. 2. Powers MA e al. Diabetes Care. 2020:43:1636-1649, N
3.htps:fprofessional.diabotes orgistes/dofaul/fies/modia/ices_and_dsmes_promotional_Ayurpel. 4. Krall JS et al. Sci Diabetos Self Manag Caro. 2021477484. PeerView.com
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
Lifestyle Modifications?1+4
“Lifestyle modifications” mea
Look AHEAD study A practical starting point
Referral to diabetes
fferent things in different contexts
Frequent, educator or clinical
aes 5 multidisciplinary Walking 175 or nutritionist
Significant time ; À
eb em counseling and more minutes (Physician referral/
follow-up per week endorsement is the
appointments strongest predictor that
a patient will go!)
1. Look AHEAD Research Group at al. Obesty (Siver Spring). 2006:14:737-752. 2. Powers MA e al. Diabetes Care. 2020:43:1636-1649, N
3.htps:fprofessional.diabotes orgistes/dofaul/fies/modia/ices_and_dsmes_promotional_Ayurpel. 4. Krall JS et al. Sci Diabetos Self Manag Caro. 2021477484. PeerView.com
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Cutting Through the Confusion About Dietary Advice: American
Society of Preventive Cardiology Clinical Practice Statement!
Weight loss/weight Manage/avoid
maintenance diabetes
Eat less ...
Eat more ... + Saturated fat
Polyunsaturated fats + Trans fats
Dietary omega3 >> ¿———— + Dietary cholesterol
+ Dietary fiber + Sodium
Phytonutrients + Galories (for weight loss)
Refined carbohydrates
QO ©
OS € PRA
pe to
a o 5
Manage/avoid Manage/avoid
hypertension dyslipidemia
1.Bolardo D et al Am J Prev Carl, 2022:10 100825. PeerView.com
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
Society of Preventive Cardiology Clinical Practice Statement!
Weight loss/weight Manage/avoid
maintenance diabetes
Eat less ...
Eat more ... + Saturated fat
Polyunsaturated fats + Trans fats
Dietary omega3 >> ¿———— + Dietary cholesterol
+ Dietary fiber + Sodium
Phytonutrients + Galories (for weight loss)
Refined carbohydrates
QO ©
OS € PRA
pe to
a o 5
Manage/avoid Manage/avoid
hypertension dyslipidemia
1.Bolardo D et al Am J Prev Carl, 2022:10 100825. PeerView.com
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
Follow-Up Visit:
BMI: 31.2 kg/m? (| 0.7 kg/m2); height: 71 inches
(180 cm); weight 224 Ib (102 kg) (| 5 Ib [2.3 kg])
AIC: 6.8% (| 0.1%); BP: 134/80 mmHg (previously
136/82 mmHg)
Medical history: obesity, hypertension, T2DM (5 y),
suspected OSA
— Gradually increasing weight, glycemia, and BP
in the last 3 y
Current medications
— Metformin 1,000 mg/sitagliptin 100 mg
combination tablet, once daily
- Losartan 50 mg, once daily
PeerView.com/USQ827
imon Kowalski, a Man Aged 47 Years
Patient Notes
Electrician from Staten Island, NY
Divorced with two adult children (one is
married and the other in college)
Ex-wife used to tell him his snoring was
“very bad”
Visit Notes
+ Disappointed with results from lifestyle
modifications
PeerView.com
Copyright © 2000-2024, PeerView
BMI: 31.2 kg/m? (| 0.7 kg/m2); height: 71 inches
(180 cm); weight 224 Ib (102 kg) (| 5 Ib [2.3 kg])
AIC: 6.8% (| 0.1%); BP: 134/80 mmHg (previously
136/82 mmHg)
Medical history: obesity, hypertension, T2DM (5 y),
suspected OSA
— Gradually increasing weight, glycemia, and BP
in the last 3 y
Current medications
— Metformin 1,000 mg/sitagliptin 100 mg
combination tablet, once daily
- Losartan 50 mg, once daily
PeerView.com/USQ827
imon Kowalski, a Man Aged 47 Years
Patient Notes
Electrician from Staten Island, NY
Divorced with two adult children (one is
married and the other in college)
Ex-wife used to tell him his snoring was
“very bad”
Visit Notes
+ Disappointed with results from lifestyle
modifications
PeerView.com
Copyright © 2000-2024, PeerView
How Effective Is Intensive Lifestyle Intervention in PwT2DM?
Lessons From the Look AHEAD Study?
Minimal Long-Term Change in A1C*
Glycated Hemoglobin
Controt_
1a
b
er Intervention
Estimated Mean, %
Estimated Mean, kg
Main effect: 0.22 (95% Ci, -0.28 0.0.16)
P< 00
7. 2 aaa 68 7 8 8 m
Modest Long-Term Change in Weight’?
Weight
Intervention
Main effect 4 (95% Cl, -$to 3)
woh P< 001
__ _— nn
7 7 2 3 a à Ww
Timo, y
u Dse
EN] 136%
Ez 23%
No statistically significant between-group difference in CV events, despite improvements in all CV risk factors except LDL-C
2 N 25,145 patents wäh TZOM and overweight or obesity folowed for up to 13. years. * P< 05 fo the between-group comparison,
1: Look AHEAD Research Group. N Engl J Med 2013;369: 145-154. 2. Wadden TA et al. Obosiy (Siver Spring). 2008.17-713-722.
PeerView.com/USQ827
com
PeerView.com
Copyright © 2000-2024, PeerView
Lessons From the Look AHEAD Study?
Minimal Long-Term Change in A1C*
Glycated Hemoglobin
Controt_
1a
b
er Intervention
Estimated Mean, %
Estimated Mean, kg
Main effect: 0.22 (95% Ci, -0.28 0.0.16)
P< 00
7. 2 aaa 68 7 8 8 m
Modest Long-Term Change in Weight’?
Weight
Intervention
Main effect 4 (95% Cl, -$to 3)
woh P< 001
__ _— nn
7 7 2 3 a à Ww
Timo, y
u Dse
EN] 136%
Ez 23%
No statistically significant between-group difference in CV events, despite improvements in all CV risk factors except LDL-C
2 N 25,145 patents wäh TZOM and overweight or obesity folowed for up to 13. years. * P< 05 fo the between-group comparison,
1: Look AHEAD Research Group. N Engl J Med 2013;369: 145-154. 2. Wadden TA et al. Obosiy (Siver Spring). 2008.17-713-722.
PeerView.com/USQ827
com
PeerView.com
Copyright © 2000-2024, PeerView
Clinical Implications of the Intervention Used
in the Look AHEAD Study’?
Amount and Durability of Weight Loss, by Category
100
e — Intensive lifestyle
a intervention
2 80 =-- Diabetes support and
3 education
5 0%-5% loss
OS oS
E as
&
$ >
5 40 } 25% loss
ae a .
5 a
¿at 210% loss
E newee" 2 +
2 TSH 215% loss
0 q T 7
1 4 8
Time, y
LL Wacéen TA ta. Obesty (Sor Sprig). 2000;17:712-722. 2, en TA etal. Obesty (ver Spring). 2011:19:1987-1900, A
3: Look AHEAD Research Group. Obesity Sivor Spring). 2014/22 5-19. 4. hips:ldiabetes orgcod-nutron PeerView.com
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
in the Look AHEAD Study’?
Amount and Durability of Weight Loss, by Category
100
e — Intensive lifestyle
a intervention
2 80 =-- Diabetes support and
3 education
5 0%-5% loss
OS oS
E as
&
$ >
5 40 } 25% loss
ae a .
5 a
¿at 210% loss
E newee" 2 +
2 TSH 215% loss
0 q T 7
1 4 8
Time, y
LL Wacéen TA ta. Obesty (Sor Sprig). 2000;17:712-722. 2, en TA etal. Obesty (ver Spring). 2011:19:1987-1900, A
3: Look AHEAD Research Group. Obesity Sivor Spring). 2014/22 5-19. 4. hips:ldiabetes orgcod-nutron PeerView.com
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Greater Weight Loss Is Associated With Greater Improvements
in CV Risk Factors: Tirzepatide SURPASS 1-414
7 AIC
.
z
3 ss $
ts 61 3
55
Time,
hr Weightloss <5%
w, Weight
” 4
5
6 se
o so
»
1
»
LRrE TT Tr
Timo, wh
+ Weight loss 5%-<10%
Systolic Blood Pressure, mmHg
us
&
3
SBP
[ZEIT
Time, wk
427
125
A Weightloss 10%-<15%
ltacanalyss I 4 RCTs of tizepati In irchviduals wih T2DM al doses of 5-15 mg, 40-42 weeks.
2200.
{Males MT ot: Dabeies Caro 208346 2202
PeerView.com/USQ827
Lipids (TG)
10
E les 176
Sm
156
ge
wo
pes m
Em 121
w
EXIT)
Time, wk
—e- Weightloss 215%
PeerView.com
Copyright © 2000-2024, PeerView
in CV Risk Factors: Tirzepatide SURPASS 1-414
7 AIC
.
z
3 ss $
ts 61 3
55
Time,
hr Weightloss <5%
w, Weight
” 4
5
6 se
o so
»
1
»
LRrE TT Tr
Timo, wh
+ Weight loss 5%-<10%
Systolic Blood Pressure, mmHg
us
&
3
SBP
[ZEIT
Time, wk
427
125
A Weightloss 10%-<15%
ltacanalyss I 4 RCTs of tizepati In irchviduals wih T2DM al doses of 5-15 mg, 40-42 weeks.
2200.
{Males MT ot: Dabeies Caro 208346 2202
PeerView.com/USQ827
Lipids (TG)
10
E les 176
Sm
156
ge
wo
pes m
Em 121
w
EXIT)
Time, wk
—e- Weightloss 215%
PeerView.com
Copyright © 2000-2024, PeerView
Higher GLP-1 RA Doses Are Associated With Higher Probability
of Reaching “ABC” Targets: SUSTAIN Evidencet.2.>
=Comparators =Semaglutide0.5mg = Semaglutide 1.0 mg
& 90
E ze 81 82
9 80
# 70
8 60
E 50
So + Semaglutide reduced
E 32 the risk of MACE by
= 30 24 26% in SUSTAIN 6 and
8 20 di 21% in PIONEER 6
E 10 + Reductions are similar
“ef AC Non-HDL Metabolic ni
<T% <140 em Cholesterol Composite AIC and waiving GUS)
<130 mg/dL —
Targets ]
2 SUSTAIN 1-57-10, and SUSTAIN China. Metabo composte endpoinsdefod as AIG <7% (<53 mmalmo), load pressure <140190 mig and non HOL colesterol <130 mg.
AL et al bios Obes Metab. 2028126239241, 2. Maso SP eral.NEnglJMod 2010378.1854.1644, 3. Husain Metal M Eng! Md 2010384841 ST ei
4. Meli LG ot al Eur Hoar J. 2024,45:1371-1374.5, Husain Met al. Diabetes Obes Metab. 2020:22:442-451. PeerView.com
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of Reaching “ABC” Targets: SUSTAIN Evidencet.2.>
=Comparators =Semaglutide0.5mg = Semaglutide 1.0 mg
& 90
E ze 81 82
9 80
# 70
8 60
E 50
So + Semaglutide reduced
E 32 the risk of MACE by
= 30 24 26% in SUSTAIN 6 and
8 20 di 21% in PIONEER 6
E 10 + Reductions are similar
“ef AC Non-HDL Metabolic ni
<T% <140 em Cholesterol Composite AIC and waiving GUS)
<130 mg/dL —
Targets ]
2 SUSTAIN 1-57-10, and SUSTAIN China. Metabo composte endpoinsdefod as AIG <7% (<53 mmalmo), load pressure <140190 mig and non HOL colesterol <130 mg.
AL et al bios Obes Metab. 2028126239241, 2. Maso SP eral.NEnglJMod 2010378.1854.1644, 3. Husain Metal M Eng! Md 2010384841 ST ei
4. Meli LG ot al Eur Hoar J. 2024,45:1371-1374.5, Husain Met al. Diabetes Obes Metab. 2020:22:442-451. PeerView.com
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Effects of GLP-1 and GIP/GLP-1-Based Therapies
on Kidney Function?
Semaglutide slowed the
Tirzepatide slowed the eGFR decline rate when assessed
rate of decline in eGFR in by both creatinine- and cystatin C-based eGFR?
the FLOW trial®
y
: ER ee
“ = ES vs insulin glargine
E 3 En
E semegiaido À i”
E 5 E
= g Sn
5. $
z I»
É pr Placebo $ so
O As
D E Insulin glargine 5 Insulin glargine
E or
ae EB E 2 e Baseline 24 wk 52wk Baseline 24 wk 52 wk
GLP-1 RAs, GIP/GLP-1 RAs, and Nephropathy Risk
& Meta-analyses of RCTs show that GLP-1 RAs lead to a large reduction in risk of albuminuria and composite
renal endpoints excluding albuminuria (doubling of serum creatinine, GFR reduction of 30%, end-stage renal
disease, or renal death)'?
1. Gone) Je a. Diabetologia 202306:1832-1945.2,Karatasis Pet al Diabetes Obes Meta. 2024:26 1090-1104. 3, Heerspink HL eta. Diabetes Cae a
2023:46.1801-1505. 4. Gragnano F etal. Cardhovasc Pharmacother, 2024;107-9. 5. Perkov Vet al. N Engl Mod. 2024:391:100-121 PeerView.com
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
on Kidney Function?
Semaglutide slowed the
Tirzepatide slowed the eGFR decline rate when assessed
rate of decline in eGFR in by both creatinine- and cystatin C-based eGFR?
the FLOW trial®
y
: ER ee
“ = ES vs insulin glargine
E 3 En
E semegiaido À i”
E 5 E
= g Sn
5. $
z I»
É pr Placebo $ so
O As
D E Insulin glargine 5 Insulin glargine
E or
ae EB E 2 e Baseline 24 wk 52wk Baseline 24 wk 52 wk
GLP-1 RAs, GIP/GLP-1 RAs, and Nephropathy Risk
& Meta-analyses of RCTs show that GLP-1 RAs lead to a large reduction in risk of albuminuria and composite
renal endpoints excluding albuminuria (doubling of serum creatinine, GFR reduction of 30%, end-stage renal
disease, or renal death)'?
1. Gone) Je a. Diabetologia 202306:1832-1945.2,Karatasis Pet al Diabetes Obes Meta. 2024:26 1090-1104. 3, Heerspink HL eta. Diabetes Cae a
2023:46.1801-1505. 4. Gragnano F etal. Cardhovasc Pharmacother, 2024;107-9. 5. Perkov Vet al. N Engl Mod. 2024:391:100-121 PeerView.com
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
FLOW Trial: Semaglutide Reduced the Risk of Kidney
Disease Events and CV Death in PwT2DM and CKD
wow Genie First Major Kidney Disease Event First Kidney-Specific Component Event
first RCT of a GLP-1 ls 35 ] HR 0.78 95% C1 066-088) | E] nr 2070 05% 01, 086098)
RA with a primary en) ae a
kidney endpoint les 2 E
rls »
0 #
N = 3,534 PWT2DM ® y Go
and CKD = gr
© Fo
Intervention: > =
semaglutide . 2
1.0 mg vs placebo ” Somaglutide o ‘Semaglutide
i A e e ser ee
Primary outcome: Time Since Randomization, mo Time Since Randomization, mo
f
nm aaa es The risk of a primary-outcome event was 24% lower in the semaglutide
lll group vs placebo group, and results were similar for a composite of the
morbidity and mortality kidney specific components of the primary outcome. Serious
AEs were also lower for semaglutide (49.6%) vs placebo (53.8%).
1. Perkovie V tal N Engl Mod. 2024:391:109:121, PeerView.com
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
Disease Events and CV Death in PwT2DM and CKD
wow Genie First Major Kidney Disease Event First Kidney-Specific Component Event
first RCT of a GLP-1 ls 35 ] HR 0.78 95% C1 066-088) | E] nr 2070 05% 01, 086098)
RA with a primary en) ae a
kidney endpoint les 2 E
rls »
0 #
N = 3,534 PWT2DM ® y Go
and CKD = gr
© Fo
Intervention: > =
semaglutide . 2
1.0 mg vs placebo ” Somaglutide o ‘Semaglutide
i A e e ser ee
Primary outcome: Time Since Randomization, mo Time Since Randomization, mo
f
nm aaa es The risk of a primary-outcome event was 24% lower in the semaglutide
lll group vs placebo group, and results were similar for a composite of the
morbidity and mortality kidney specific components of the primary outcome. Serious
AEs were also lower for semaglutide (49.6%) vs placebo (53.8%).
1. Perkovie V tal N Engl Mod. 2024:391:109:121, PeerView.com
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
Switching Between GLP-1-Based Medications’?
+ Patients may need to switch from one agent to
another or restart therapy after an interruption
— Insurance changes or drug shortages
— Higher-efficacy agent is needed
— Suspending/resuming medication in the context of surgery
+ Patients may need slower uptitration to avoid AEs
This activity includes a practice aid that explains
+ Comparative doses for interchanging GLP-1 RAs
+ How to implement extended-interval dosing
1. Wiiey HP etal. Cin Pharmacol Updates. 2023:41:457-473. 2. hips: www asaha orgabou-asairewsroomVnews-leases/2023:06/amercansocety-a- —
anesthes'ologists-consensus-based-guidance-on-preoperaive. 3, his /issuu.com/anapublshing docs/anesthesia_care_of_the_patent_on_a_gp-1 receptor. PeerView.com
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
+ Patients may need to switch from one agent to
another or restart therapy after an interruption
— Insurance changes or drug shortages
— Higher-efficacy agent is needed
— Suspending/resuming medication in the context of surgery
+ Patients may need slower uptitration to avoid AEs
This activity includes a practice aid that explains
+ Comparative doses for interchanging GLP-1 RAs
+ How to implement extended-interval dosing
1. Wiiey HP etal. Cin Pharmacol Updates. 2023:41:457-473. 2. hips: www asaha orgabou-asairewsroomVnews-leases/2023:06/amercansocety-a- —
anesthes'ologists-consensus-based-guidance-on-preoperaive. 3, his /issuu.com/anapublshing docs/anesthesia_care_of_the_patent_on_a_gp-1 receptor. PeerView.com
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
Safety Considerations for Approved Injectable
GLP-1 RAs and GIP/GLP-1 RAs for T2DM
Agent Common AE
Dulaglutide: Nausea, diarrhea, vomiting, Pancreatitis, hypoglycemia, hypersensitivity reactions, acute kidney injury, severe Gl
5 abdominal pain, decreased appetite disease, monitor retinopathy, acute gallbladder disease, evaluate benefit vs risk in pregnancy
Acute pancreatitis, hypoglycemia, acute kidney injury, severe Gl disease, immunogenicity-
Exenatide ER? Injection-site nodule, nausea associated decreased glycemic control, hypersensitivity reactions, thrombocytopenia, serious
ISRs, acute gallbladder disease, evaluate benefit vs risk in pregnancy
Nausea, diarrhea, vomiting,
Liraglutide? decreased appetite, dyspepsia,
‘constipation
Acute pancreatitis, hypoglycemia, acute kidney injury, hypersensitivity reactions,
acute gallbladder disease, evaluate benefit vs risk in pregnancy
Pancreatitis, monitor retinopathy, hypoglycemia, acute kidney injury, hypersensitivity
reactions, acute gallbladder disease, evaluate benefit vs risk in pregnancy, discontinue use in
women at least 2 months before a planned pregnancy
Pancreatitis, hypoglycemia, hypersensitivity reactions, acute kidney injury, severe Gl
disease, monitor retinopathy, acute gallbladder disease, may cause fetal harm, females using
(OCs should switch to non-OC method or use a barrier method for 4 weeks after initiation and
each dose increase
Nausea, vomiting, diarrhea,
Semaglutidet hdominal pain, constipation
Nausea, diarrhea, decreased
Tirzepatides appetite, vomiting, constipation,
dyspepsia, abdominal pain
All are associated with thyroid C-cell tumors (in rodents) and are contraindicated
patients with a personal or family history of MTC or MEN2
1. Trey (dolido) Prescrpton Information. tos www accessdata fda goviérugstida_docsfabol2022/125469505 bp.
2 Brdureon BGse (exenaide) Prescripion nformaton. Nits: accessdata {8a govlcragsatiéa_docs/ebel2024/2082 1050230 pl
3. Via (raglutde) Prescription Information. hips www accessdata160.qovÍdrgsatia,docsfabel023/02234 180304 pt
4. Ozenpi magic) Prvepton oration pew acera cn porton coer 272200972021 few:
3 Mounier (rcpt) Proscspoon Information pe nn accassónt Ida Gevcrageatdn,docsfabel 20237 188880. 00230060 pal PeerView.com
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
GLP-1 RAs and GIP/GLP-1 RAs for T2DM
Agent Common AE
Dulaglutide: Nausea, diarrhea, vomiting, Pancreatitis, hypoglycemia, hypersensitivity reactions, acute kidney injury, severe Gl
5 abdominal pain, decreased appetite disease, monitor retinopathy, acute gallbladder disease, evaluate benefit vs risk in pregnancy
Acute pancreatitis, hypoglycemia, acute kidney injury, severe Gl disease, immunogenicity-
Exenatide ER? Injection-site nodule, nausea associated decreased glycemic control, hypersensitivity reactions, thrombocytopenia, serious
ISRs, acute gallbladder disease, evaluate benefit vs risk in pregnancy
Nausea, diarrhea, vomiting,
Liraglutide? decreased appetite, dyspepsia,
‘constipation
Acute pancreatitis, hypoglycemia, acute kidney injury, hypersensitivity reactions,
acute gallbladder disease, evaluate benefit vs risk in pregnancy
Pancreatitis, monitor retinopathy, hypoglycemia, acute kidney injury, hypersensitivity
reactions, acute gallbladder disease, evaluate benefit vs risk in pregnancy, discontinue use in
women at least 2 months before a planned pregnancy
Pancreatitis, hypoglycemia, hypersensitivity reactions, acute kidney injury, severe Gl
disease, monitor retinopathy, acute gallbladder disease, may cause fetal harm, females using
(OCs should switch to non-OC method or use a barrier method for 4 weeks after initiation and
each dose increase
Nausea, vomiting, diarrhea,
Semaglutidet hdominal pain, constipation
Nausea, diarrhea, decreased
Tirzepatides appetite, vomiting, constipation,
dyspepsia, abdominal pain
All are associated with thyroid C-cell tumors (in rodents) and are contraindicated
patients with a personal or family history of MTC or MEN2
1. Trey (dolido) Prescrpton Information. tos www accessdata fda goviérugstida_docsfabol2022/125469505 bp.
2 Brdureon BGse (exenaide) Prescripion nformaton. Nits: accessdata {8a govlcragsatiéa_docs/ebel2024/2082 1050230 pl
3. Via (raglutde) Prescription Information. hips www accessdata160.qovÍdrgsatia,docsfabel023/02234 180304 pt
4. Ozenpi magic) Prvepton oration pew acera cn porton coer 272200972021 few:
3 Mounier (rcpt) Proscspoon Information pe nn accassónt Ida Gevcrageatdn,docsfabel 20237 188880. 00230060 pal PeerView.com
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
Case Conclusion:
imon Kowalski, a Man Aged 47 Years
BMI: 32 kg/m? R Switch to
Height: 71 inches (180 cm) Tirzepatide 2.5 mg > 5 mg
Weight: 224 Ib (102 kg) or
AIC: 6.8% Semaglutide 0.25 mg > 1.0 mg
BP: 134/80 mmHg (Coadministration of GLP-1 RAs or GIP/GLP-1
Suspected OSA RAs with DPP-4is may increase the risk of
adverse events without increasing efficacy)
— Gradually increasing weight, glycemia, and BP
in the last 3 y
Current medications
- Metformin 1,000 mg/sitagliptin 100 mg What patient characteristics
combination tablet, once daily would change your treatment
— Losartan 50 mg, once daily recommendation?
PeerView.com
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
imon Kowalski, a Man Aged 47 Years
BMI: 32 kg/m? R Switch to
Height: 71 inches (180 cm) Tirzepatide 2.5 mg > 5 mg
Weight: 224 Ib (102 kg) or
AIC: 6.8% Semaglutide 0.25 mg > 1.0 mg
BP: 134/80 mmHg (Coadministration of GLP-1 RAs or GIP/GLP-1
Suspected OSA RAs with DPP-4is may increase the risk of
adverse events without increasing efficacy)
— Gradually increasing weight, glycemia, and BP
in the last 3 y
Current medications
- Metformin 1,000 mg/sitagliptin 100 mg What patient characteristics
combination tablet, once daily would change your treatment
— Losartan 50 mg, once daily recommendation?
PeerView.com
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
Applying the “3Es” to Manage GI AEs in Patients Using
GIP/GLP-1 RAs or GLP-1 RAs
Education and Escalation to an
Explanation Appropriate Dose
Effective Management
of GIAEs
Provide anticipatory
guidance on GI AEs and
dietary modifications
If mild: increase water
and fiber intake
Gradually uptitrate per PI
If persistent or severe:
rule out underlying
Gi disorders
Consider slower schedule
if tolerability is an issue
AEs typically mild-to-
moderate and transient
1. Wharton eta. Postgrod Med, 2022;134:1,14:19.2. Gorgojo-Martnez JJ et al. J Cin Med. 2022:12 146. PeerView.com
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
GIP/GLP-1 RAs or GLP-1 RAs
Education and Escalation to an
Explanation Appropriate Dose
Effective Management
of GIAEs
Provide anticipatory
guidance on GI AEs and
dietary modifications
If mild: increase water
and fiber intake
Gradually uptitrate per PI
If persistent or severe:
rule out underlying
Gi disorders
Consider slower schedule
if tolerability is an issue
AEs typically mild-to-
moderate and transient
1. Wharton eta. Postgrod Med, 2022;134:1,14:19.2. Gorgojo-Martnez JJ et al. J Cin Med. 2022:12 146. PeerView.com
PeerView.com/USQ827 Copyright © 2000-2024, PeerView
Establishing a “Virtuous Cycle” in
Comprehensive T2DM and Obesity Management'
Use shared
decision-making to
choose which goal
to pursue first
Set Develop a
‘ manageable Intervention
ser ee to is altempted
Elia reach goals
1. Vals M. tnt Gin rect 2016:70:198:205. 2. Matze LS otal. Patent 2022:15:367-377.
PeerView.com/USQ827
In a clinical trial program
for a GIP/GLP-1 RA
therapy in PwT2DM,
improved glycemic
control and reduced
weight was associated
with adoption of other
healthful behaviors
(dietary modifications,
increased exercise)
- > Plan is
working
Distress is
reduced;
meaningful
benefits are
noticed
Encourages
‘adherence
to plan
PeerView.com
Copyright © 2000-2024, PeerView
Comprehensive T2DM and Obesity Management'
Use shared
decision-making to
choose which goal
to pursue first
Set Develop a
‘ manageable Intervention
ser ee to is altempted
Elia reach goals
1. Vals M. tnt Gin rect 2016:70:198:205. 2. Matze LS otal. Patent 2022:15:367-377.
PeerView.com/USQ827
In a clinical trial program
for a GIP/GLP-1 RA
therapy in PwT2DM,
improved glycemic
control and reduced
weight was associated
with adoption of other
healthful behaviors
(dietary modifications,
increased exercise)
- > Plan is
working
Distress is
reduced;
meaningful
benefits are
noticed
Encourages
‘adherence
to plan
PeerView.com
Copyright © 2000-2024, PeerView
Key Takeaways
Patients have fewer complications with early management of glycemia and weight
A nutritious diet and physical activity are foundational to healthy living, but may
have only modest effects on glycemia, weight, and other aspects of T2DM
GIP/GLP-1 RAs and GLP-1 RAs are the most effective agents for addressing A1C
and weight and have favorable effects on other CV risk factors
T2DM is a self-managed disease: use diabetes self-management education (DSME)
and support to help patients set reasonable, achievable goals
PeerView.com/USQ827
PeerView.com
Copyright © 2000-2024, PeerView
Patients have fewer complications with early management of glycemia and weight
A nutritious diet and physical activity are foundational to healthy living, but may
have only modest effects on glycemia, weight, and other aspects of T2DM
GIP/GLP-1 RAs and GLP-1 RAs are the most effective agents for addressing A1C
and weight and have favorable effects on other CV risk factors
T2DM is a self-managed disease: use diabetes self-management education (DSME)
and support to help patients set reasonable, achievable goals
PeerView.com/USQ827
PeerView.com
Copyright © 2000-2024, PeerView
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