Treat the thrinity Semaglutide From Theory to Practice (3).pptx

Significantly lower rate of mean annual eGFR decline with semaglutide compared with placebo in the overall population
ETD (semaglutide vs placebo): 0.59 mL/min/1.73 m² [95% CI: 0.29−0.89]; P 0.05)�
No increase in risk for AEs and no new safety concerns were identified with semaglutide

1. From Theory to Practice: Oral semaglutide in Patient Care Speaker details

2. Financial Disclosure The speaker has been commercially supported by Novo Nordisk for this promotional meeting, in return for providing a service, and has no actual or potential conflict of interest in relation to this presentation *The information, advocacy, suggestions and/or updates provided during the scheduled webinar is not intended or implied to be directed towards HCPs practicing outside the geographical territory of India

3. 4 Patient journey Recently diagnosed T2D with weight issues T2D with CVD T2D with CKD on insulin All images are for representation purpose only

4. 4 Patient journey Recently diagnosed T2D with weight issues T2D with CVD T2D with CKD on insulin All images are for representation purpose only

5. Recently Diagnosed T2D with Weight Issues All images are for representation purpose only

6. Potential Benefits of Oral Semaglutide When Initiated Early 6 8 out of 10 patients achieved glycemic target of <7% when oral semaglutide is initiated within 1 year of T2D diagnosis Achieve Glycemic target Sustained glycemic control Effective weight loss Diabetes remission 1 in 3 patients achieved a glycemic target of <6% and weight loss of > 5% when initiated within 1 year of diagnosis >50% of patients achieved pharmacological remission when oral semaglutide was added to their existing therapy within 10 years of T2D diagnosis More patients on GLP-1RA therapy maintained glycemic targets of <7% when initiated early compared to other OADs All images are for representation purpose only

7. Early Initiation of Oral Semaglutide in T2DM: Achievement of Clinically Relevant Targets Data are for the trial product estimand . BW, Body weight; HbA1C, glycated haemoglobin; sema , semaglutide Goldenberg R et al. Can J Diabetes. 2021; 45(7):S28-29 Early Initiation of oral semaglutide within ≤1 year of T2D diagnosis resulted in a high proportion of patients achieving glycaemic targets , including near-normal HbA1c, as well as composite endpoints for glycaemic control plus weight loss. HbA 1c <7.0% Oral semaglutide 14 mg Placebo Diabetes duration ≤1 year Proportion of patients (%) HbA 1c <6.0% plus body weight loss ≥5% Oral semaglutide 14 mg Placebo Proportion of patients (%) Start Early with Oral Semaglutide in T2D to achieve Near-Normal HbA1c, Effective Weight Loss, Fewer Complications Proven Results in newly diagnosed Patients

8. More No. Of. Patients Achieved Weight Loss of >5% with Oral Semaglutide Data are observed proportions for the trial product estimand (on trial product without rescue medication). *p<0.0001 for the EOR with oral semaglutide 14 mg vs placebo. †p<0.0001 for the EOR with oral semaglutide 14 mg vs the active comparator. EOR, estimated odds ratio. 1. Aroda VR, et al. Diabetes Care. 2019;42:1724–32; 2. Rodbard H, et al. Diabetes Care. 2019;42:2272–81; 3. Rosenstock J, et al. JAMA. 2019;321:1466–80; 4. Pratley R, et al. Lancet. 2019;394:39–50; 5. Mosenzon O, et al. Lancet Diabetes Endocrinol. 2019;7:515–27; 6. Zinman B, et al. Diabetes Care. 2019;42:2262–71. 1 in 2 patients achieved >5% weight loss 1 in 5 patients achieved >10% weight loss

9. Oral Semaglutide Reduces Body Weight Through Appetite Suppression *p<0.05 CVD, cardiovascular disease; GLP-1, RAs, glucagon-like peptide-1 receptor agonists; kJ, kilojoules; T2D, type 2 diabetes; vs, versus 1. Blundell J et al. Diabetes Obes Metab 2017;19:1242–1251; 2. Rodbard HW et al. Diabetes Care 2019;42:2272–2281; 3. Rosenstock J et al. JAMA 2019;321:1466–1480; 4. Zinman B et al. Diabetes Care 2019;42:2262–2271. Semaglutide also reduced waist circumference , an independent predictor of atherosclerotic CVD risk, at 26 weeks 2–4 Oral Semaglutide –3.7 cm* Empagliflozin -3.0 cm vs Oral Semaglutide –2.3 cm* Sitagliptin -0.6 cm vs Oral Semaglutide –3.6 cm* Placebo -0.7 cm vs Add-on to insulin Energy intake and food consumption are reduced with semaglutide vs placebo relative difference in energy intake 35% Energy intake during ad libitum lunch 1 vs Semaglutide 2,378 kJ* Placebo 3,634 kJ Scored better on questions related to food cravings, control eating and portion size, while still feeling meals were pleasant 1 vs Semaglutide Placebo

10. Slim Down Effectively: Oral Semaglutide Helps to Reduce Fat Mass While Preserving Muscle Mass 10 Oral semaglutide exerted beneficial effects on body weight and body composition by reducing fat mass and improving muscle mass . Study design: 26-weeks, open-label, real-life prospective study Subjects: Thirty-two patients (age ≥18 years) with established diagnosis of type 2 diabetes and obesity Dosage Oral semaglutide administered 3 mg daily for 30 days, 7 mg daily from second month till end 1. Volpe S, et al. Front Endocrinol (Lausanne). 2023 Sep 13;14:1240263.   BMI, body mass index; FMI, fat mass index; FFMI, fat free mass index; SMI, skeletal muscle mass index; SMM, skeletal muscle mass; VAT, visceral adipose tissue. Values are expressed as percent change from baseline (T0). Change versus T0: *p<0.05; **p<0.001 Changes in Anthropometric Parameters After 6 Months Therapy ** * ** Body weight ( 75.3 kg) BMI (28.2 kg/m2) Waist circumference ( 102.1 cm) FFMI SMI SMM/VAT VAT Changes in Body Composition After 6 Months Therapy **

11. GLP-1RA is More Effective in Achieving and Maintaining Target HbA1c Levels When Initiated Early HbA1c, glycated haemoglobin ; SU, Sulphonylureas ; GLP-1RA, Glucagon like peptide 1 receptor agonist; T2DM Type 2 Diabetes 1. Kaneto H et al. Int J Mol Sci. 2021;22(15):7917. 2. Folz R et al. Diabetologia. 2021;64(10):2131-2137; 3. Shibeshi MS et al. BMC Endocr Disord . 2022;22(1):161; 4. Eliaschewitz FG et al. Diabetol Metab Syndr . 2021;13(1):99. 5. GRADE Study Research Group, N Engl J Med. 2022; 387:1063-1074. Risk of a primary-outcome event (HbA1C>7%) was significantly lower with GLP-1RA than with Sulphonylureas or DPP4i (p<0.05) when started early 5 Early Initiation Early GLP-1RA use in T2DM is advised for glycemic control plus weight loss & beta-cell protection. 1-2 Prevent complications Achieving good glycemic control early is crucial to prevent retinopathy, nephropathy, and neuropathy 3 Legacy effects Arteriosclerosis prevention 1,2 & cardiovascular metabolic safety 4,5 DPP4i SU GLP-1RA Insulin

12. Pharmacological Remission (A1C<6.5% with Pharmacotherapy) with Oral Semaglutide When Added to Existing Therapy in T2D 12 The SGLT2i plus semaglutide group exhibited a significant reduction after 6 months body mass index, fasting plasma glucose, HbA1C Lunati ME et al. Pharmacol Res. 2024;199:107040 . ACR albumin/creatinine ratio; BMI, body mass index; FPG, Fasting Plasma Glucose; HbA1c, glycated hemoglobin ; T2DM, type 2 diabetes mellitus. . Achieving HbA1c < 6.5%: SGLT2i Group: 22.7% (94/415) of subjects SGLT2i + Sema Group: 51.8% (282/544) of patients Achievement of HbA1c < 6.5%, suggesting a pharmacological remission of T2D with Oral Semaglutide 2X Improvement of HbA1c in T2D with addition of Oral Semaglutide 2X 2X Study Design Observational, real-world study Participants 1335 patients with type 2 diabetes SGLT2i Alone: 443 patients SGLT2i and oral semaglutide : 892 patients

13. Early Initiation of Oral Semaglutide in T2DM: Real-world Evidence from Ongoing PIONEER REAL India Study DebmalyaSanyal et al, A real-world evidence study investigating clinical parameters associated with the usage of once-daily oral semaglutide in adults with type 2 diabetes: Baseline characteristics from the PIONEER REAL India study, poster presented at ESICON 2023 Oral semaglutide has been well accepted as the preferred drug for managing early diabetes in India 1 in 5 were started on oral semaglutide within 1 year of diagnosis A1c 8.9% Mean baseline indicating poor glycemic control 1 in 2 participants had CVD related history stressing the need for effective treatment options 90% were started for achieving better glycemic and weight control Inclusion criteria: With T2, Aged ≥ 18 years, HbA1c value ≤ 9% Injectable GLA naïve Exclusion Prior or current use of oral semaglutide, Prior participation SAMPLE size: 387 Primary endpoint Change in HbA1c (v1v3) Secondary endpoints Change in body weight Proportion of people achieving HbA1c <7% at V3 Oral Semaglutide o nce daily Wk 1 to Wk 33 Wk Wk 34 to Wk 44 V1 V2 if applicable V3, End of study visit Observation period PIONEER REAL study

14. RIGHT from START: Oral Semaglutide is Now Approved for 1st Line Management of T2DM in India First Line Approval: Secured DCGI (Drug Control General of India) approval for first-line indication of management of T2DM in Jan 2024 5 th Country to receive the approval Oral Semaglutide Redefining type-2 diabetes care In India Oral Semaglutide is indicated Oral Semaglutide is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus to improve glycemic control as an adjunct to diet and exercise > 18 years of age First line Monotherapy/ combination use Special populations (hepatic & renal impairment) Cardiovascular safe

15. Potential Benefits of Oral Semaglutide When Initiated Early 15 8 out of 10 patients achieved glycemic target of <7% when oral semaglutide is initiated within 1 year of T2D diagnosis Achieve Glycemic target Sustained glycemic control Effective weight loss Diabetes remission 1 in 3 patients achieved a glycemic target of <6% and weight loss of > 5% when initiated within 1 year of diagnosis >50% of patients achieved pharmacological remission when oral semaglutide was added to their existing therapy within 10 years of T2D diagnosis More patients on GLP-1RA therapy maintained glycemic targets of <7% when initiated early compared to other OADs All images are for representation purpose only

16. 4 Patient journey Recently diagnosed T2D with weight issues T2D with CVD T2D with CKD on insulin All images are for representation purpose only

17. T2D with Cardiovascular Disease All images are for representation purpose only

18. Potential Benefits of Oral Semaglutide in Patients with T2D and CVD 18 Weight reduction of up to 5 kg 5 kg 1.5% HbA1c reduction of up to 1.5% Waist circumference up to 4.7 cm 4.7cm Systolic BP reduction of up to 5 mmHg 5 mmHg CV risk factors Reduction of LDL, TG, hsCRP levels 18 21% Proven CV safety & 21% MACE reduction* All images are for representation purpose only * Non-significant

19. Greater Proportion Achieved Target A1C of <7% with Oral Semaglutide 8.0 8.1 8.3 8.0 8.0 8.3 8.2 PIONEER 1 Monotherapy 26 weeks PIONEER 2 vs empagliflozin 52 weeks PIONEER 3 vs sitagliptin 78 weeks PIONEER 4 vs liraglutide 52 weeks PIONEER 5 Renal 26 weeks PIONEER 7 Flex 52 weeks PIONEER 8 With insulin 52 weeks * * * * * * * vs pbo * * * * * Proportion of subjects (%) Sema 3 mg Sema 7 mg Sema 14 mg Pbo Sema 14 mg Empa 25 mg Sema 3 mg Sema 7 mg Sema 14 mg Sita 100 mg Sema 14 mg Lira 1.8 mg Pbo Sema 14 mg Pbo Sema Flex Sita 100 mg Sema 3 mg Sema 7 mg Sema 14 mg Pbo Mean baseline HbA 1c , % ~7 out of 10 patients achieve HbA1c <7% with Oral Semaglutide *p<0.05 for odds of achieving HbA1c <7.0% with oral semaglutide vs placebo or active comparator. Flex, flexible; Empa , empagliflozin; Lira, liraglutide; Pbo , placebo; Sema , semaglutide; Sita, sitagliptin. Aroda VR, et al. Diabetes Care 2019;42:1724–32; Rodbard HW, et al. Diabetes Care 2019;42:2272–2281; Rosenstock J, et al. JAMA 2019;321:1466–80; Pratley R, et al. Lancet 2019;394:39–50; Mosenzon O, et al. Lancet Diabetes Endocrinol 2019;7:515–27; Pieber TR, et al. Lancet Diabetes Endocrinol 2019;7:528–39; Zinman B et al. Diabetes Care 2019;42:2262–2271.

20. Oral Semaglutide Reduces Systolic Blood Pressure Mean change from baseline ( mmHg ) Each 10 mmHg decrease in mean systolic blood pressure is associated with reductions in risk in people with T2D † 11% for any complication related to diabetes 16% for deaths related to diabetes 11% for myocardial infarction 10% for microvascular complications T2D, type 2 diabetes. Husain M et al. N Engl J Med 2019;381:841–51; Stratton IM et al. Diabetologica 2006;8:1761-9. Oral Semaglutide Improves systolic blood pressure by offering a reduction of ~1- 6 mmHg

21. Oral Semaglutide Improves Blood Lipids LDL, low-density lipoprotein. Husain M et al. N Engl J Med 2019;381:841–51 . Change ratio to baseline Change in ratio to baseline Oral Semaglutide Improves lipid profile with reduction in LDL and TG levels

22. Oral Semaglutide Reduces Vascular Inflammation CRP is a biomarker of CV risk and is produced in response to: 1 Tissue injury Inflammation Infection CRP Change from baseline in hsCRP (%) Oral sema 14 mg Empa 25 mg Oral semaglutide vs empagliflozin 52 weeks CRP, C-reactive protein; CV, cardiovascular; Empa , empagliflozin; hsCRP , high-sensitivity C-reactive protein; Pbo , placebo; sema , semaglutide. 1. Ridker PM. Circulation 2020;141:787‒9; 2. Rosenstock JR et al. Presented at the 70th American College of Cardiology Annual Scientific Session, 15–17 May 2021.

23. Semaglutide Consistently Reduced the Risk of MACE 1. Husain M, et al. Diabetes Obes Metab 2020;22(3):442–451. In SUSTAIN and PIONEER combined, semaglutide showed consistent effects with 24% significant risk reduction in MACE versus comparators across varying CV risk Favours Semaglutide Favours comparator Favours Semaglutide Favours placebo HR [95% CI] 0.74 [0.58;0.95] 0.79 [0.57;1.11] 0.76 [0.62;0.92] SUSTAIN 6 + PIONEER 6 Risk reduction 26% 21% 24% PIONEER 6 SUSTAIN 6 Time to first MACE CV death Non-fatal stroke Non-fatal MI * Three-component MACE included CV death, nonfatal MI, and nonfatal stroke. CI, confidence interval; CV, cardiovascular; HR, hazard ratio; MACE, major adverse cardiovascular events; PIONEER, Peptide Innovation for Early Diabetes Treat ; SUSTAIN, Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes; T2DM, type 2 diabetes mellitus. * sub-cutaneous Semaglutide is not available in India

24. Reduction in Cardiovascular & All-cause Mortality with Oral Semaglutide HR, hazard ratio. Husain M et al. N Engl J Med. 2019. 381:841–51. Promising CV safety with 49% all cause mortality & 51% CV death reduction for non-inferiority

25. SOUL: Ongoing Oral semaglutide Cardiovascular & Renal Outcome Trial in T2D CVD, cardiovascular disease; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; FPFV, first patient first visit; MACE, major adverse cardiovascular event; SoC, standard of care (will allow all glucose-lowering drugs except GLP-1RAs); MALE, major adverse limb events; PAD, Peripheral Artery Disease;  SGLT2, sodium-glucose transport protein 2 ; SOUL, Semaglutide cardiovascular outcomes trial in patients with type 2 diabetes; T2DM, type 2 diabetes mellitus. End of treatment Oral Semaglutide 14 mg OD + SoC Placebo + SoC Duration: up to 5 years (1,225 events) Randomization (1:1) 9,642 patients with T2D ≥50 years Established CVD or CKD HbA1c 6.5–10% Primary 1,2 Demonstrate that oral semaglutide lowers the risk of 3-point MACE vs placebo Secondary 1,2 Compare the effect of oral semaglutide vs placebo for:  CKD CV events PAD & MALE Glycaemic control Body weight Safety Exploratory 2 Compare the effect of oral semaglutide vs placebo for: Cognitive function Smoking Trial information FPFV 17-Jun-2019 Double blinded Superiority study Slightly larger proportion of men (71.1 % vs 54-69% in earlier trials) ~ 800 patients from India Proportion of HF patients at baseline (23% vs 10-14.8 % earlier trials) Sizeable proportion participants treated with SGLT-2 inhibitors at baseline (26.7 % vs 1-15% earlier trials) Less usage of sulfonylureas (29.1 % vs 25-50 % earlier) Unique differences in baseline characteristics vs. earlier studies 1. Clinicaltrials.gov: NCT03914326; 2. ClinicalTrials.gov. SOUL. Available at: https://clinicaltrials.gov/ct2/show/NCT03914326. Accessed March 2023.; 3. SOUL trial protocol V4.0, Novo Nordisk, data on file.

26. Guidelines Recommend Use of GLP-1RAs like Semaglutide as First Line in T2D with CVD or High CV risk Diabetes Care. 2024 Jan 1;46(Supplement_1):S140-S157.

27. Potential Benefits of Oral Semaglutide in Patients with T2D and CVD 27 Weight reduction of up to 5 kg 5 kg 1.5% HbA1c reduction of up to 1.5% Waist circumference up to 4.7 cm 4.7cm Systolic BP reduction of up to 5 mmHg 5 mmHg CV risk factors Reduction of LDL, TG, hsCRP levels 27 21% Proven CV safety & 21% MACE reduction* All images are for representation purpose only * Non-significant

28. 4 Patient journey Recently diagnosed T2D with weight issues T2D with CVD T2D with CKD on insulin All images are for representation purpose only

29. T2D with Chronic Kidney Disease on Insulin All images are for representation purpose only

30. Potential Benefits of Oral semaglutide in T2D with CKD on Insulin Therapy 1 5 2 4 3 Reduction of total daily insulin dose by 20% Direct and indirect nephroprotective effects No weight gain & weight loss up to 4.2 kg in Pts on insulin Robust Glycemic and weight reduction in CKD Additional A1c reduction of up to 1.2% in Pts on insulin Low risk of severe hypoglycemic episodes & MACE reduction in CKD All images are for representation purpose only

31. GLP-1RAs May Exert Beneficial Nephroprotective Outcomes GLP-1RAs, Glucagon-like peptide 1 receptor agonists; MCP-1, monocyte chemoattractant protein-1; RAAS, renin-angiotensin-aldosterone system; TNF, tumour necrosis factor, 1. Muskiet MHA et al. Nat Rev Nephrol 2017;13:605–28; 2. Gorriz JL et al. J Clin Med. 2020;9:947.http://dx.doi.org/10.3390/jcm9040947. Potential mechanism of action of GLP-1RAs in kidney Direct effects Kidney and systemic inflammation (reduced plasma levels of TNF α, MCP1) •O 2 – •OH Oxidative stress Reduced Increased Natriuresis Na + Indirect effects Improved Glycaemic control Blood pressure control Weight control

32. Impact of Oral Semaglutide on Glycemia And Weight Loss Remains Significant In Patients With T2D And Reduced eGFR, Contributing To CKD Prevention And Lower Renal Complication Risks Glycaemic efficacy of semaglutide is sustained in people with moderately to severely decreased kidney function *eGFR <60 ml/min per 1.73 m 2 ; † ETD, -0.8%; 95% CI, -1.0 to -0.6; p<0.0001; ‡ Semaglutide is not recommended in patients with end-stage renal disease. eGFR, estimated glomerular filtration rate; ETD, estimated treatment difference; HbA 1c , haemoglobin A 1c ; PwT2D, people with type 2 diabetes; OD, once daily; SGLT-2, sodium-glucose co-transporter-2 1. Mosenzon O, et al. Lancet Diabetes Endocrinol. 2019;7:515-27. 2. Semaglutide ( Rybelsus ® ) Summary of Product Characteristics, last revised October 2023. Oral Semaglutide’s effect on glycemia and body weight reductions remains prominent in PwT2D and moderately to severely decreased eGFR* 1 Oral semaglutide significantly decreased HbA 1c versus placebo in PwT2D and renal impairment 1 Semaglutide 14 mg † Placebo -1.0% -0.2% Change in HbA 1c OD ORAL No dose adjustment of OD semaglutide ‡ is required in PwT2D 32 Oral semaglutide significantly decreased body weight versus placebo in PwT2D and renal impairment 1 Semaglutide 14 mg † Placebo -3.4 Kg -0.9 Kg Change in Body weight OD ORAL baseline: 90.8 kg baseline: 8.0 % PIONEER 5 study design T2D ≥90 days eGFR 30–59 mL/min/1.73 m 2 Randomised, double-blind Oral Semaglutide vs placebo N= 324

33. Semaglutide Offers A Significantly Smaller Annual Decline In Kidney Function, Providing Superior Renal Protection For Patients With T2DM. AE, adverse event; CI, confidence interval; CV, cardiovascular; CVOT, cardiovascular outcomes trial; eGFR, estimated glomerular filtration rate; EOT, end of treatment; ETD, estimated treatment difference; GLP-1RA, glucagon-like peptide-1 receptor agonist; HR, hazard ratio; N, number of participants; OD, once-daily; OW, once-weekly; s.c. , subcutaneous; T2DM, type 2 diabetes mellitus. Tuttle K, et al. Kidney Int 2022 Semaglutide was associated with a significantly smaller annual decline in kidney function compared with placebo People with type 2 diabetes at high cardiovascular risk treated with semaglutide experience more stable kidney function compared with placebo Cohort GLP-1RA CVOTs (populations with T2D at high CV risk) SUSTAIN 6 PIONEER 6 Semaglutide N=3 239 Placebo N=3 241 OW s.c. : 0.5 and 1.0 mg OD oral: 14 mg Volume-matched placebo Pooled by treatment Pooled by treatment Methods Post hoc analyses Pooled data by treatment OVERALL Semaglutide vs Placebo eGFR SUBGROUPS 30−<60 mL/min/1.73 m² Semaglutide vs Placebo or ≥60 mL/min/1.73 m² Semaglutide vs Placebo Endpoints Annual change in eGFR (eGFR slope) from baseline to EOT Time to persistent eGFR reduction of ≥30%, ≥40%, ≥50%, or ≥57% Significantly lower rate of mean annual eGFR decline with semaglutide compared with placebo in the overall population ETD ( semaglutide vs placebo): 0.59 mL/min/1.73 m² [95% CI: 0.29−0.89]; P < 0.0001 No significant interaction (P = 0.10) between treatment effect and eGFR subgroups Numerically largest ETD in the 30−<60 mL/min/1.73 m² eGFR subgroup: ETD: 1.06 mL/min/1.73 m² [95% CI: 0.45−1.67]; P = 0.0007 HRs for time to persistent eGFR decline in the overall population were <1.0 (all P > 0.05) No increase in risk for AEs and no new safety concerns were identified with semaglutide Outcomes Post hoc analysis of SUSTAIN 6 and PIONEER 6: semaglutide provides more stable kidney function in high-risk T2DM patients compared to placebo. * sub-cutaneous Semaglutide is not available in India

34. Oral Semaglutide Effectively Improves eGFR and Reduces UACR In T2D with CKD HbA1c, glycated haemoglobin; eGFR, estimated glomerular filtration rate; UACR: urinary albumin to creatinine ratio. 1. Medicina 2019, 55, 233. 2. Yanai H et al. Cardiol Res. 2022;13(5):303-308.

35. GLP-1RAs have Shown Significant MACE Risk-reduction in CVOTs, Consistent Across Baseline Kidney Function *All trials, except ELIXA, had three-point MACE as the primary endpoint; in ELIXA the primary endpoint was an expanded four-point composite outcome including hospital admission for unstable angina. CI, confidence interval; CVOTs, cardiovascular outcome trials; eGFR, estimated glomerular filtration rate; GLP-1RAs, glucagon-like peptide-1 receptor agonists; MACE, major adverse cardiovascular event, Sattar N et al. Lancet Diabetes Endocrinol 2021;9:653–62. Meta-analysis of GLP-1RA CVOTs Cardiovascular outcomes* GLP-1RAs provide a cardiovascular benefit that appears to be consistent regardless of baseline eGFR <60 mL/min/1.73m 2 HR: 0.88 (95% CI: 0.77; 1.01) ≥60 mL/min/1.73m 2 HR: 0.83 (95% CI: 0.74; 0.93) 12% Reduction in risk of 3-point MACE 17% Reduction in risk of 3-point MACE 14% Overall population HR: 0.86 (95% CI: 0.80; 0.93); p<0.0001 Reduction in risk of 3-point MACE P interaction =0.52

36. Guidelines Recommend Use of GLP-1 RAs in T2D with CKD for Additional Glucose Control / Persistent Albuminuria *ACEi or ARB should be first-line therapy for hypertension when albuminuria is present. † Finerenone is currently the only nonsteroidal MRA with proven clinical kidney and cardiovascular benefits. ACE, angiotensin-converting enzyme inhibitor; ACR, Albumin/Creatinine Ratio; ARB, angiotensin II receptor blocker; ASCVD, atherosclerotic cardiovascular disease; BP, blood pressure; CGM, Continuous glucose monitoring; DPP-4, dipeptidyl peptidase-4; eGFR, estimated glomerular filtration rate; GLP-1RA, glucagon-like peptide 1 receptor agonist; HbA1c, glycosylated hemoglobin; SGLT-2, sodium glucose co-transporter-2 inhibitor; T2D, type 2 diabetes; TZD, thiazolidinediones. KDIGO Diabetes Work Group. Kidney Int 2022;102:S1–S127 . Lifestyle KDIGO guidelines First-line drug therapy Physical activity Smoking cessation Weight management Regular risk factor reassessment (every 3-6 months) T2D only All patients (T1D and T2D) Healthy diet Targeted therapy ASCVD risk, lipids Moderate-or high-intensity statin HbA 1c , CGM Metformin (if eGFR ≥30) SGLT2i (Initiate eGFR ≥20; continue until dialysis or transplant) BP Urine ACR RAS inhibitor at maximum tolerated dose (if HTN*) Dihydropyridine CCB and/or diuretic if needed to achieve individualised BP target Steroidal MRA if needed for resistant hypertension if eGFR ≥45 Ezetimibe, PCSK9i, or icosapentethyl if indicated based on ASCVD risk and lipids Antiplatelet agent for clinical ASCVD Nonsteroidal MRA † if persistent albuminuria and normal potassium Other glucose-lowering drugs if needed to achieve individualised glycaemic target GLP-1RA if needed to achieve individualised glycaemic target or if persistent albuminuria

37. Study design: RCT (PIONEER 8) Subjects 731 patients (age ≥18 years) T2DM ≥90 days Stable treatment Basal insulin Basal and bolus insulin Premixed insulin HbA1c 7.0–9.5% Greater Proportions of Patients on Insulin Achieved Glycemic Target with Lower Risk of Weight gain/Hypoglycemia when Oral Semaglutide is Added Observed data from the in-trial observation period. Data are for the treatment policy estimand (evaluates the treatment effect regardless of premature trial product discontinuation or use of rescue medication), for the full analysis set. *p<0.001 based on the odds ratio versus placebo. HbA1c, glycated hemoglobin ; PIONEER, Peptide Innovation for Early Diabetes Treatment; RCT, randomized controlled trial; T2DM, type 2 diabetes mellitus. Aroda V, et al.. Canadian Journal of Diabetes. 2022 Nov 1;46(7):S5-6; Poster 721-P presented at the American Diabetes Association 82nd Scientific Sessions, June 3–7, 2022, virtual and in-person (New Orleans, Louisiana, USA) meeting * Greater HbA1c <7% No Body Weight Gain No Hypoglycemic Events† Placebo Oral semaglutide

38. Glycemic and Weight Reduction of Oral Semaglutide as Add on to Insulin Change in HbA1c *p< 0.0001; HbA 1c , glycated haemoglobin ; IAsp , insulin aspart ; Oral sema , oral semaglutide; s.c. subcutaneous; sema , semaglutide. 1. Zinman B et al. Diabetes Care. 2019; 42:2262-2271; 2. Rodbard HW et al. J Clin Endocrinol Metab . 2018; 103(6):2291-2301; 3. Kellerer M et al. Diabetes Obes Metab . 2022; 10.1111/dom.14765 PIONEER 8 1 Baseline HbA 1c ; 8.2% (66 mmol/mol) (basal, basal-bolus, or premixed insulin) o ral sema 3 mg o ral sema 7 mg o ral sema 14 mg placebo C hange from baseline (%) * * * PIONEER 8 1 Baseline bodyweight; 85.9 kg (basal, basal-bolus, or premixed insulin) o ral sema 14 mg placebo o ral sema 3 mg o ral sema 7 mg * * Change from baseline (kg) * Change in Body weight

39. Insulin Sparing Effect and Safety of Oral Semaglutide in T2D Patients on Insulin Observed data from the in-trial observation period. Data are for the treatment policy estimand (evaluates the treatment effect regardless of premature trial product discontinuation or use of rescue medication), for the full analysis set. *p<0.001 based on the odds ratio versus placebo. Aroda V, et al.. Canadian Journal of Diabetes. 2022 Nov 1;46(7):S5-6; Poster 721-P presented at the American Diabetes Association 82nd Scientific Sessions, June 3–7, 2022, virtual and in-person (New Orleans, Louisiana, USA) meeting Proportion of patients (%) Proportion of patients with severe or BG-confirmed symptomatic hypoglycemia Proportion of patients achieving insulin dose reduction of ≥20% sema 3 mg sema 7 mg sema 14 mg placebo

40. Potential Benefits of Oral semaglutide in T2D with CKD on Insulin Therapy 1 5 2 4 3 Reduction of total daily insulin dose by 20% Direct and indirect nephroprotective effects No weight gain & weight loss up to 4.2 kg in Pts on insulin Robust Glycemic and weight reduction in CKD Additional A1c reduction of up to 1.2% in Pts on insulin Low risk of severe hypoglycemic episodes & MACE reduction in CKD All images are for representation purpose only

41. 4 Patient journey Recently diagnosed T2D with weight issues T2D with CVD T2D with CKD on insulin All images are for representation purpose only

42. Thank you