LANDMARC meeting SIE or FGM H2 2024.pptx

LANDMARC meeting SIE or FGM H2 2024 sanofi

1. LANDMARC MEETING Translating learnings from LANDMARC into real practice This event is only for invited and registered medical practitioners MAT-IN-2400977-V1.0-07/2024

2. The need for LANDMARC Longitudinal real-world diabetes studies in India: ‘Need of the Hour’! LANDMARC is the first large- scale, longitudinal, prospective, observational real- world study to investigate management & complications in type 2 diabetes across India over a period of 3 years 1 363 Sites 6234 patients Reveals impact and long- term consequences of T2DM in India Provides unprecedented real- world insights into diabetes management in India Offers nationwide perspective on diabetes- related complications & glycemic control LANDMARC KEY OUTCOMES “ “ ‘Unmet need ’ in India diabetes studies are limited to cross- sectional population-based surveys, which only determine the prevalence of the disease.

3. LANDMARC: First of its kind nationwide longitudinal real-world study 382 Sites Screened N=6279 Evaluable at baseline N=6222 Evaluable at 3-year N=5273 Inclusion criteria T2D: duration ≥2 years Age at diagnosis ≥25 to ≤60 years Antidiabetic agents ≥2 T1D/secondary diabetes Limited life expectancy Exclusion criteria CV death (n=37) Voluntary withdrawal (n=54) Site withdrawal (n=169) Death by other reason (n=16) Lost to follow-up (n=394) Other (n=291) Discontinued study (n=961) Eligibility criteria failure (n=44) Withdrew consent (n=1) CV, cardiovascular; T1D, type 1 diabetes mellitus; T2D, type 2 diabetes mellitus. Objective: To determine the occurrence of diabetes complications, glycemic control, and treatment patterns in the routine clinical practice over a period of 3 years.

4. Endpoints HbA1c, glycated hemoglobin; OAD, oral antidiabetic drugs . Complication Endpoints Proportion of participants with macrovascular disease over 36 months Development of microvascular complications at 12, 24, and 36 months Proportion of participants with cumulative incidence of composite events and other cardiovascular events Glycemic Control Endpoints Proportion of participants controlled (HbA1c <7% and <6.5%) at the end of 6, 12, 24, and 36 months Participants with controlled (HbA1c <7%) and uncontrolled (HbA1c ≥7%) disease at the end of 36 months Comparison of the Glycemic control and outcomes at 36 months between participants with and without complications at baseline Management Endpoints Time to treatment adaptation from baseline to 12, 24, and 36 months (any dose change/ addition/ deletion/ drug intensification/ titration for OADs, insulin or other injectable antidiabetic agents)

5. Duration of disease (years), median (range) 7.1 (4.3-11.1) Duration of disease (years) 2-6   2359 (37.8) 6-10 2147 (34.4) >10 1728 (27.7) Cities   Metro 2376 (38.1) Non-metro 3858 (61.9) Treatment   Insulin 1549 (24.8) Insulin-naive 4685 (75.2) Cardiovascular risk factors N=3282 Hypertension 2566 (78.2) Dyslipidemia 1636 (49.8) Albuminuria 153 (4.7) Family history of PCD 65 (2.0) Age (years), mean (SD) 52.1 (9.15) Age group (years)   ≤30 61 (1.0) 31-49 2192 (35.2) 50-65 3552 (57.0) ≥66 429 (6.9) Gender, n (%)   Male 3526 (56.6) Female 2708 (43.4) BMI (N=6215), mean (SD) 27.2 (4.6) BMI group (kg/m 2 )   Underweight 44 (0.7) Normal 903 (14.5) Overweight 1119 (18.0) Obese 4149 (66.8) HbA1c (%), mean (SD) 8.1 (1.6) Glycemic status (N=4477)   < 7.0 % 1121 (25.0) ≥ 7.0 % 3356 (75.0) Demographics: Overall Data shown as n (%), unless otherwise specified. HbA1c, glycated hemoglobin; PCD, premature coronary disease; SD, standard deviation; HTN - Hypertension. Parameters Participants (N=6234) Parameters Participants (N=6234) Avg age 52 years > 65% patients were Obese 4-11 years of T2DM duration 75% were on OADs alone 75% of patients had uncontrolled glycemia HTN and dyslipidemia in > 50%

6. Snapshot of real-world profile of Diabetic patient in India The mean age was 52.1 years , with 35% in the working age group, underscoring potential workplace productivity challenges due to T2DM. An average disease duration of 8.6 years. A BMI of 27.2 kg/m 2 and 2/3 rd being obese flags obesity as a significant comorbidity needing concurrent management. 75% having unregulated glycemia underlines the pressing need for more effective blood sugar management tools and awareness. 2.3% faced macrovascular issues, mainly non- fatal myocardial infarction , while 14.5% had microvascular complications, predominantly neuropathy. Approximately 75% of T2DM patients relying on multiple OADs emphasize the immediate need for early combination therapy and insulin usage to overcome clinical inertia. High prevalence of hypertension and dyslipidemia reported, imposing grave cardiovascular risks among the participants.

7. Complication Endpoints The Hidden Toll : Uncontrolled Glycemia and the Cumulative Complication Burden

8. Proportion of participants with macrovascular disease over 36 months (N=6222) Data shown as n (%), unless otherwise specified. 216 macrovascular complications Over 3 years, macrovascular complications increased 2.3 to 3.3% 2/3 rd Non-fatal MI  Parameters Baseline 36 months (n=6222) Total number of macrovascular complications 148 216 Total number of participants with macrovascular complications 144 (2.31) 205 (3.29) New complications over 36 months - 68 Non-fatal myocardial infarction 74 (51.39) 82 (40.00) Non-fatal stroke 29 (20.14) 32 (15.61) Cardiovascular death 37 (18.05) Peripheral vascular disease 45 (31.25) 63 (30.73) No macrovascular complications 5935 - Unknown 143 -

9. Microvascular complications at 12, 24 and 36 months Data shown as n (%). months 12 months 24 months 36 Total number of microvascular complications Total number of participants with complications Neuropathy Nephropathy Retinopathy 735 ( 81.67 ) 154 ( 17.11 ) 1147 815 1276 894 221 161 1313 919 (81.98) 229 (20.43) 165 (14.72) Baseline 1030 900 (14.46) 141 ( 15.67 ) 180 152 1121 (18.02) Over 3 years M icrovascular complications increased – 14.5% to 18% Neuropathy was the most common (n=919, 81.98% )

10. The Sugar Coaster: Tracking Glycemic Control over Three Years Glycemic Control

11. HbA1c, glycated hemoglobin. Proportion of participants who are controlled (HbA1c <7%) at the end of 36 months A trend of improvement was seen in the glycemic control over 3-years of study duration However, at the end of 3 years a significant proportion of participants i.e. 63.4 % did NOT reach HbA1C target of <7%

12. HbA1c, glycated hemoglobin. Occurrence of complications in participants with controlled (HbA1c <7%) and uncontrolled (HbA1c ≥7%) disease at the end of 36 months H igher proportion of uncontrolled diabetes, 78.2% and 70.3% was seen in participants who developed macrovascular or microvascular complications respectively than in participants without complications Any macrovascular complications No complications Any microvascular complications

13. * p=0.0039; # p<0.0001 FPG, fasting plasma glucose; HbA1c, glycated hemoglobin; PPG, postprandial glucose. Participants with any macrovascular complications Participants without any macrovascular complications A) B) Glycemic control at 36 months in participants with and without macrovascular complications at baseline  Among participants without macrovascular complications at baseline , there was a significant increase in the proportion of participants reaching HbA1c <7% at the end of 36 months # *

14. # p<0.0001 HbA1c, glycated hemoglobin. Participants with any microvascular complications # Participants without any microvascular complications A) B) # Glycemic control at 36 months in participants with and without microvascular complications at baseline  Among participants without microvascular complications at baseline , there was a significant increase in the proportion of participants reaching HbA1c <7% at the end of 36 months

15. Vicious cycle of Uncontrolled glycemia-Complication-Uncontrolled glycemia Majority of patients had uncontrolled glycemia Patients with diabetic complications encountered greater challenges in reaching their target glycemic levels. Higher risk of developing diabetic complications Due to greater challenge in achieving glycemic target ther e is uncontrolled glycemia leading to more complications 01 02 04 03 How do we break this cycle?

16. Treatment Landscape: Evolving Antidiabetic Therapies and use of insulins Therapy

17.   OAD, oral antidiabetic agents. M ajority of the participants were taking only OADs (baseline 67.66% to 36 months 73.86%) Addition of injectables (mostly insulin) was preferred in participants who were only on OADs at baseline. O ral and injectable anti-diabetic drugs categories The participants already on a combination of OADs and injectables had minimal shifts in their treatment and tended to continue with their ongoing combination of treatment. P articipants on injectables, showed h a lf of the participants (50.69%) continuing with basal insulin, and 37.77% and 14.04%   of participants continuing with premix insulin and prandial insulin, respectively, over 36 months treatment period. 01 02 03 04

18. 30.4% 29 % 17%     Antidiabetic drug count   1 OAD 2 OADs 3 OADs 4 OADs 5 OADs >5 OADs   244 (3.9) 2887 (46.4) 2011 (32.3) 814 (13.1) 185 (3.0) 55 (0.9) Insulin [n=1541] 234 (15.2) 567 (36.8) 464 (30.1) 194 (12.6) 48 (3.1) 8 (0.5) Insulin naïve [n=4681] 10 (0.2) 2320 (49.6) 1547 (33.0) 620 (13.2) 137 (2.9) 47 (1.0)  222 (3.6) 1928 (31.0) 2010 (32.3) 1228 (19.7) 425 (6.8) 158 (2.5)  Insulin [n=1541] 172 (11.2) 443 (28.7) 440 (28.6) 272 (17.7) 91 (5.9) 22 (1.4) Insulin naïve [n=4681] 50 (1.1) 1485 (31.7) 1570 (33.5) 956 (20.4) 334 (7.1) 136 (2.9)   249 (4.0) 1674 (26.9) 1902 (30.6) 1208 (19.4) 454 (7.3) 229 (3.7)  Insulin [n=1541] 160 (10.4) 415 (26.9) 401 (26.1) 259 (16.8) 95 (6.2) 40 (2.6) Insulin naïve [n=4681] 89 (1.9) 1259 (26.9) 1500 (32.0) 949 (20.3) 359 (7.7) 189 (4.0)   234 (3.8) 1458 (23.4) 1739 (27.9) 1170 (18.8) 427 (6.9) 197 (3.2)   Insulin [n=1541] 148 (9.6) 355 (23.0) 374 (24.3) 248 (16.1) 89 (5.8) 34 (2.2) Insulin naïve [n=4681] 86 (1.8) 1103 (23.6) 1365 (29.2) 922 (19.7) 338 (7.2) 163 (3.5) Data shown as n (%). Percentages are based on number of participants using at least one OAD within each subgroup in evaluable population.OAD , oral antidiabetic agents. Summary of OAD count by treatment   months 12 months 24 months 36 Baseline [N=6196] [N=5971] [N=5716] [N=5225] I ncrease in the proportion of participants taking ≥3 OADs from baseline to 36-months This highlights the overreliance on OADs in Indian Diabetic Care Visits > 3 OADs 28.9%

19. AGIs, alpha-glucosidase inhibitors; DPP-4i, dipeptidyl peptidase-4 inhibitors; GLP-1A, glucagon-like peptide-1 analog; SGLT2i, sodium glucose cotransporter 2 inhibitors 1.1 1.1 48.9 62.4 10.5 23.4 13.5 22.8 93.0 92.2 77.3 76.3 14.3 11.0 11.2 14.2 18.6 25.0 0.9 1.5 6.4 3.7 Shift in oral and injectable anti-diabetic drugs   Among orals, DPP4i , SGLT2i and AGi use increased overtime while Biguanides and SU continued to be used. The proportion of participants taking injectable glucose-lowering medications increased from 25.5% at baseline to 36.7% at 3 years . Adoption of basal insulin was the highest among injectables 25.5% at baseline to 36.7% at 3 years

20. < 3 OAD vs > 3 OAD -20 -40 -60 HbA1c FPG PPG % change (mean) - < 3 OADs > 3 OADs -0.7 -0.6 -17.6 -9.6 -28.0 -21.5 *p value is calculated for the change from the baseline using paired t-test. FPG, fasting plasma glucose; HbA1c, glycated hemoglobin; PPG, postprandial glucose; OADs, oral anti-diabetic drugs. Therapy Trends at 3-year Follow-up Glycemic parameters improved in the insulin subgroup compared to the insulin naïve subgroup (p<0.0001) No additional glycemic benefit in patients using >3 OADs vs patients using <3 OADs -0.6 Insulin naive Insulin * p<0.001 -20 -40 -60 HbA1c FPG PPG * * * % change (mean) - -1.1 -14.0 -24.4 -23.3 -38.8 Insulin vs Insulin naive

21. FPG, fasting plasma glucose; HbA1c, glycated hemoglobin; PPG, postprandial glucose; OADs, oral anti-diabetic drugs. Therapy Trends at 3-year Follow-up Glycemic parameters were similar after 3 years in the Basal insulin vs Premix Insulin subgroup. Basal Insulin vs Premix Insulin -20 -40 -60 HbA1c FPG PPG % change (mean) - Basal Insulin Premix Insulin -1.1 -1.1 -25.5 -26.1 -42.5 -36.0 Basal insulin Premix Insulin Baseline (SD 95% CI) 3 year (SD 95% CI) Baseline (SD 95% CI) 3 year (SD 95% CI) FPG (mg/dl) 155.7 (151.1, 160.2) 128.4 (125.2,131.6 ) 156.8 (151.6,162) 131 (127.2,134.8) PPG (mg/dl) 226.3 (219.9,232.7) 183.5 (179.4,187.7) 226.7 (219.7,233.7) 188.7 (183.2,194.2) HbA1c (%) 8.7% 7.6% 8.7% 7.6%

22. Therapeutic Management over a 3-year period ≤3 OAD users showed significant FPG improvement vs. >3 OAD users (P=0.0030). No significant difference in HbA1c and PPG levels between ≤3 and >3 OAD subgroups. Basal insulin prefered by 22.78% of participants. Premix insulin was choice of 14.25% participants. Insulin Choices: Comparing Basal and Premix OAD Optimization: Glycemic controls Timely intensification of therapy , such as initiation of insulin , may help improve glycemic parameters.

23. Translating learnings from LANDMARC into real practice

24. Rapidly Diminishing Efficacy of Newer Oral Antidiabetic Drugs – Attributed to Progressive β -cell Loss In a meta-analysis by Avogaro et al., DPP4 inhibitors showed an apparent accepted mean increase in HbA1c of 0.22% after 52 weeks of usage. Loss of glucose lowering efficacy after 2 years of treatment was observed with dapagliflozin A declining efficacy for SGLT2 inhibitors was also observed in a meta-analysis by Monami et al. over 104 weeks Decreasing efficacy of OADs Reference: Hanefeld M, et al. Diabetes Ther . 2020 Aug;11(8):1645–1666. Overreliance on OADs is problematic, underscoring the need for timely insulin initiation and treatment intensification

25. Multifaceted Benefits of Timely Initiation of Insulin Therapy Preserves β -cell mass and function Effectively controls the glucotoxic effects of hyperglycemia Improves insulin sensitivity Protects against endothelial dysfunction and damage that cause vascular disease Provides long-term protection to end organs via ‘metabolic memory’ Alters the course of disease progression in a positive manner Reference : Owens D. Diabetes Technol Ther . 2013;15(9):776–785.

26. Gla-100 Can Be a Solution to Tackle I nadequate Insulinisation!! Gla-100 regimen is Kalra S, et al. Indian J Endocrinol Metab . 2016;20(3):408–411. Freeman JS. J Am Osteopath Assoc . 2009;109(1):26 – 36.   Flexible 1 Gla-100 provides mealtime flexibility as it involves only one injection per day and does not require adherence to a strict meal pattern. 1 Glargine can be injected at any time of the day, at the same time each day. 1 Simple 1 Less intrusive 1 Mimic physiological insulin 2 Hence, Gla-100 would be the ideal insulin to initiate in diabetic patients

27. High Proportion Of Patient Achieving Glycemic Target With Gla-100 With Minimal Weight Gain LIVE INDIA: Effectiveness of Gla-100 in a Post hoc Pooled Analysis of FINE ASIA and GOAL Registries Primary objective: To assess the change in HbA1c from baseline to 6 months in insulin-naive participants with T2DM treated with Gla-100 in the Indian subgroups of FINE ASIA and GOAL studies. Secondary objectives: To evaluate the changes in: fasting plasma glucose (FPG) body weight insulin dose To assess the incidence of hypoglycemia Patients: 955 (males 547) Mean Age: 54.7 (9.8) BMI: 27.4 HTN 87.4% & Dyslipidemia 73.5% HbA1c 9.54% (1.5) FPG 215.5 mg/dl (68.8) FPG Reference: Deshmukh, Vaishali, et al. Diabetes Therapy  14.12 (2023): 2075-2088.

28. Results of LIVE India Study . Absolute Change in HbA1c from Baseline Change in HbA1c Levels patients reached HbA1c targets of <7.0% after 6 months. patients reached HbA1c targets of <7.5% after 6 months. 30.6% 61.7% Reference: Deshmukh, Vaishali, et al. "LIVE INDIA: Effectiveness of Gla-100 in a Post hoc Pooled Analysis of FINE ASIA and GOAL Registries."  Diabetes Therapy  14.12 (2023): 2075-2088. Baseline 3 months 6 months -2.1 % at 6 months (SD 1.4; 95% CI - 2.2 to - 2.0) -1.3 % at 3 months (SD 1.3; 95% CI -1.4 to-1.3) HbA1c % 9.54 8.2 7.5

29. Results of LIVE India Study -0.1 kg ( SD 3.8; 95% CI - 0.3 to 0.2 ) in 6 months Change in Body Weight Baseline: 15.7 (7.3) U 3 months: 17.3 (8.0) U 6 months: 18.2 (8.9) U Change in dose in 6 months: 2.5 (SD 5.6; 95% CI 2.1 to 2.8) (p<0.05) Change in Gla-100 Dose Body weight Mean change: -0.1 kg Change in insulin glargine 100 U/ml dose Mean change: 2.5 U/day (up-titration) Deshmukh, Vaishali, et al. "LIVE INDIA: Effectiveness of Gla-100 in a Post hoc Pooled Analysis of FINE ASIA and GOAL Registries."  Diabetes Therapy  14.12 (2023): 2075-2088.

30. Insulin Gla-100 vs. Premix Insulins* Sethi B, et al. Diabetes Ther . 2022;13(8):1409–1481.​ * Human Premix Gla-100: Insulin glargine 100; HbA 1c : Glycated hemoglobin. HbA 1c   ​ change ​ Hypoglycemic events ​ Response ​ rate ​ Weight  ​ change ​ Treatment  satisfaction ​ Gla-100 vs. premixed insulin Significantly higher HbA 1c reduction Significantly lower incidence of overall and nocturnal hypoglycemia Significant difference with respect to the proportion of patients achieving target HbA 1c Significantly less weight gain Better treatment satisfaction scores with Gla-100

31. A Basal Insulin Regimen is an Ideal Start Efficacy Safety Convenience Gla100 provides better glycemic reduction v/s Human Premix Gla100 provides similar HbA1C reduction as IDegAsp (OD) Cost Abbreviations: FFF: Fix Fasting First Gla100 causes lesser hypoglycemia and lesser weight gain v/s premixed insulins Once daily convenience of Gla100 leads to better persistence and better patient satisfaction Night-time OD basal insulin does not interfere with patients' daily routine Gla100 is one of the most affordable analog insulin Reference: Slandl E, et al. Diabetes Care. 2016 Aug:39 Suppl 2:5172-9 ; Kumar A, et al. PLoS ONE. 2016;11(10):e0163350; Janka HU, et al.. Diabetes Care. 2005;28:254–9; Sethi B, et al. Diabetes Ther. 2022;13(8):1409–1481; Basur O et al et al. Clinicoecon Outcomes Res 2013;5:497-505; Sethi B, et al. Diabetes Ther . 2022;13(8):1409–1481 For other insulin brands, MRP as on May’23 from 1MG.com; Gla100 has emerged over the course of time, as the ‘Gold Standard’ of Basal Insulin therapy for people with T2DM

32. Innovator Gla100 has now become more accessible Reference: 1 Parmar A, Pal A and Sharma P. National List of Essential Medicines 2022 of India: Perspectives from Psychiatrists. Indian J Psychol Med. 2023;XX:1–4. NPPA circular-CG-DL-E-01042023-244884.S.O. 1568(E) 2 Available at First long-acting insulin analogues prequalified | WHO - Prequalification of Medical Products (IVDs, Medicines, Vaccines and Immunization Devices, Vector Control) accessed on 21 st June 2023. NLEM inclusion criteria Proven safety & efficacy profile 1 A lignment with the current national practice guidelines 1 + Better access  Better care for patients Inclusion in NLEM is a testimony for product safety, efficacy and high-quality care for patients Old MRP New MRP Old MRP New MRP Innovator Gla100 3ML cartridge Innovator Gla100 Disposable Pen (3ML) ₹ ₹ ₹ ₹ -19% -30% First long-acting insulin analogues prequalified 2 WHO Prequalification list

33. Need for Insulin titration

34. Data presented with up arrow showed increased in mean insulin dose from baseline Change in dose of insulin categories There was Inadequate Up-Titration of Insulin after initiation during the 3 year follow up. Change in insulin dose from baseline to 12,24, and 36 months

35. 3 9 20 32 Insulin dose 14.2 IU 20.2 IU 22.3 IU 23.8 IU Mean HbA1c (%) Months of treatment 30-50 % T2DM patients remain uncontrolled 6 months after basal insulin initiation  because of inadequate titration Key to successful management of glycemic control is adequate titration Gla100 + OADs with adequate titration can help patients achieve sustained control for >2.5 years Polonsky WH, et al. Int J Clin. 2017;71e12973; Mockarski et al. J Manag Care Spec. Pharm. 2018; 24:390-400 1. Owens DR, et al. Diabetes Res Clin Pract . 2014;106:264–274. |. 2. Marso SP, et al. N Engl J Med. 2017;377:723–732. 3. EMA. Guidelines on clinical investigation of medicinal products in the treatment or prevention of diabetes mellitus 2012. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/06/WC500129256.pdf [Accessed April 2019].

36. The first 12 weeks can make a difference for patients with T2DM *Results from pooled analysis of 15 RCTs including 2,837 patients with T2DM ± OADs initiating insulin glargine therapy (2000–2012). 1 FPG, fasting plasma glucose; OAD, oral antihyperglycaemic drug; RCT, randomised controlled trial; T2DM, Type 2 diabetes mellitus. 1. Owens DR, et al. Diabetes Res Clin Pract . 2014;106:264–274. 2. Marso SP, et al. N Engl J Med. 2017;377:723–732. Basal insulin dose increase and glycaemic outcomes over time* 1 With effective titration, >80% of the maximum treatment effect (in terms of reductions in HbA1c) was achieved at 12 weeks after basal insulin initiation. 1 Titration period Maintenance period Baseline 0-12 weeks 12-24 weeks Dose increase 0.16 IU/Kg +0.24 IU/kg (150%) +0.05% IU/kg (12.5%) HbA1c reduction 8.8% -1.4% -0.2% FPG reduction 195.7mg/dl -74.0 mg/dl -3.2 mg/dl

37. Recommendations for Basal Insulin Initiation and Titration Bajaj S, et al. Diabetes Ther . 2019; 10:1189–1204. FPG: Fasting plasma glucose; HbA1c: Glycated hemoglobin. Initiate Initial dose: 0.1 – 0.2 U/kg/day Dose to be administered once daily, preferably at bedtime* E.g. – Basal insulin dose for 80 kg body weight – 16 IU Self-monitoring Monitor FPG values daily Generally, FPG ranging between 100mg/dL and 130 mg/dL (5.6–7.2 mmol/L) is appropriate for most circumstances Dose titration Titrate based on the average of the 3 most recent FPG values Increase dose once or twice a week if FPG is above target . Reduce dose in case of hypoglycemia Monitor HbA1c at 3 months 01 02 03 04 *While once-daily basal insulin is preferably administered at bedtime, it can be administered any time of the day depending on the sociocultural circumstances.

38. Gla-100 has proven efficacy of 20 years and has sustained Hba1c Control when initiated early and optimally titrated 1,2 Timely intensification of therapy, such as initiation of insulin, may help improve glycemic parameters High proportion of patients have unregulated glycemia, high BMI, CV Co-morbitites and Diabetic complications v Key Messages Gla-100 is easy to initiate, has a convenient once a day regime, higher DTSQ score than premix insulins 3,4 Reference: 1. Schreiber SA, et al. Diabetes Obes Metab . 2007; 9: 31-8. Schreiber SA, et al. Diabetes Technol Ther 2008;10:121-7. 2. 1.Sethi B, et al. Diabetes Ther . 2022;13(8):1409–1481 3. Reference: American Diabetes Association. Diabetes Care. 2022 Jan; 45 (Suppl. 1): S125-S143. 4. Sethi B, et al. Diabetes Ther . 2022;13(8):1409–1481 5.

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