Slide 1 American Diabetes Association 76 th Scientific Sessions Investor and analyst event New Orleans, 13 June 216 Shanghai part of Cities Changing Diabetes
Slide 2 Forward-looking statements Novo Nordisk s reports filed with or furnished to the US Securities and Exchange Commission (SEC), including the company s Annual Report 215 and Form 2-F, which are both filed with the SEC in February 216 in continuation of the publication of the Annual Report 215, and presentations made, written information released, or oral statements made, to the public in the future by or on behalf of Novo Nordisk, may contain forward-looking statements. Words such as believe, expect, may, will, plan, strategy, prospect, foresee, estimate, project, anticipate, can, intend, target and other words and terms of similar meaning in connection with any discussion of future operating or financial performance identify forward-looking statements. Examples of such forward-looking statements include, but are not limited to: Statements of targets, plans, objectives or goals for future operations, including those related to Novo Nordisk s products, product research, product development, product introductions and product approvals as well as cooperation in relation thereto Statements containing projections of or targets for revenues, costs, income (or loss), earnings per share, capital expenditures, dividends, capital structure, net financials and other financial measures Statements regarding future economic performance, future actions and outcome of contingencies such as legal proceedings, and Statements regarding the assumptions underlying or relating to such statements. These statements are based on current plans, estimates and projections. By their very nature, forward-looking statements involve inherent risks and uncertainties, both general and specific. Novo Nordisk cautions that a number of important factors, including those described in this presentation, could cause actual results to differ materially from those contemplated in any forward-looking statements. Factors that may affect future results include, but are not limited to, global as well as local political and economic conditions, including interest rate and currency exchange rate fluctuations, delay or failure of projects related to research and/or development, unplanned loss of patents, interruptions of supplies and production, product recall, unexpected contract breaches or terminations, government-mandated or market-driven price decreases for Novo Nordisk s products, introduction of competing products, reliance on information technology, Novo Nordisk s ability to successfully market current and new products, exposure to product liability and legal proceedings and investigations, changes in governmental laws and related interpretation thereof, including on reimbursement, intellectual property protection and regulatory controls on testing, approval, manufacturing and marketing, perceived or actual failure to adhere to ethical marketing practices, investments in and divestitures of domestic and foreign companies, unexpected growth in costs and expenses, failure to recruit and retain the right employees, and failure to maintain a culture of compliance. Please also refer to the overview of risk factors in Managing risks on p 42-43 of the Annual Report 215. Unless required by law, Novo Nordisk is under no duty and undertakes no obligation to update or revise any forward-looking statement after the distribution of this presentation, whether as a result of new information, future events or otherwise. Important drug information Victoza (liraglutide 1.2 mg & 1.8 mg) is approved for the management of type 2 diabetes only Saxenda (liraglutide 3 mg) is approved in the US and EU for the treatment of obesity only
Slide 3 Agenda Time 6.15 pm 6.2 pm 6.3 pm 6.4 pm 6.55 pm Topic Welcome - Early insights from Tresiba launch in the US Jakob Riis, EVP China, Pacific and Marketing SWITCH 1 and 2 - Reduced risk of hypoglycaemia with Tresiba versus insulin glargine U1 demonstrated in the SWITCH trials Peter Kristensen, SVP Global Development Faster-acting insulin aspart - Greater early glucose-lowering effect in type 1 diabetes demonstrated in clinical trials Peter Kurtzhals, SVP Global Research LEADER - Statistically significant reduction in risk of major adverse cardiovascular events with Victoza in the LEADER trial Mads Krogsgaard Thomsen, EVP and Chief Science Officer SUSTAIN 2 and 3 - Superior HbA 1c and weight reduction with once-weekly injectable semaglutide demonstrated in the SUSTAIN 2 and 3 trials and phase 2 results from oral semaglutide Alan Moses, SVP and Chief Medical Officer 7.5 pm Discussion and Q&A
Slide 4 Steady Tresiba growth trajectory in the US, while market share continues to grow in Japan despite biosimilar launch Continued steady growth in total number of Tresiba prescriptions in the US Basal Value MS 8% Tresiba Levemir glargine U1 NN total basal glargine U3 Tresiba continues to grow basal market share in Japan despite launch of biosimilar glargine Tresiba Levemir NN total basal Basal glargine U1 glargine U3 Value MS biosimilar glargine 8% 6% 4% 62% 28% 26% 6% 4% 43% 43% 35% 2% % Mar 3/1/213 213 6% 2% Apr 216 2% % Mar 213 8% 8% 2% Mar 216 Note: The graph does not show NPH, which accounts for the residual market share Source: IMS monthly data, April 216 TRx: total prescription count; MS: market share Note: The graph does not show NPH, which accounts for the residual market share Source: IMS monthly data, May 216
Slide 5 SWITCH 1 and 2 Reduced risk of hypoglycaemia with Tresiba versus insulin glargine U1 demonstrated in SWITCH trials Peter Kristensen SVP Global Development
SWITCH 2 SWITCH 1 ADA 216 investor and analyst event Slide 6 SWITCH trials aimed to investigate the reduction of hypoglycaemia with Tresiba versus insulin glargine U1 SWITCH 1 and 2 trial designs Baseline characteristics 51 people with type 1 diabetes 721 people with type 2 diabetes IDeg once daily + 2-4 x IAsp IGlar once daily + 2-4 x IAsp IDeg once daily ± OAD IGlar once daily ± OAD IDeg once daily + 2-4 x IAsp IGlar once daily + 2-4 x IAsp IDeg once daily ± OAD IGlar once daily ± OAD SWITCH 1 SWITCH 2 Mean age (years) 45.9 61.4 Mean diabetes duration (years) 23.4 14.1 Mean BMI (kg/m 2 ) 27.5 32.2 Mean HbA 1c 7.6% 7.6% Mean FPG (mmol/l) 9.4 7.6 Randomised 1:1 Double-blinded 16 weeks titration 1,2 16 weeks HbA 1c stable 16 weeks titration 1,2 16 weeks HbA 1c stable 1 SWITCH 1: 2% dose reduction of basal and bolus insulin dose; 2 SWITCH 2: 2% dose reduction if coming from previous twice-daily treatment Note: Daily injections of both Tresiba and insulin glargine evenly split between morning and evening IDeg: insulin degludec (Tresiba ) IGlar: insulin glargine U1; OAD: oral anti-diabetic; IAsp: insulin aspart Basal once daily / Basal twice daily * 44.7% / 35.7% ** 84.2% / 15.8% * In SWITCH 1, the pre-trial treatment regimen included 2-4 daily bolus insulin injections ** Does not add up to 1% as 19.4% were pump users prior trial enrollment and one patient could not be classified to a regimen BMI: body mass index; FPG: fasting plasma glucose Source: Lane et al., poster, 87-LB and Wysham et al., poster, 9-LB, ADA 216
Slide 7 Tresiba showed lower rate of hypoglycaemia than insulin glargine U1 in maintenance period in the SWITCH 1 trial 7 6 5 4 3 2 1 Severe or BG confirmed symptomatic events Cumulative events per patient 8 16 2 24 28 32 Weeks 1 Severe or BG confirmed symptomatic nocturnal events.2. 16 2 24 28 32 Weeks 1.5 Severe events Tresiba glargine U1 1.4.3 11% * 36% 1.2 * 35% **.25 lower lower lower rate 1. rate.2 rate with.8 with with Tresiba Tresiba.15 Tresiba.6.1.4. 16 2 24 28 32 Weeks 1 1 Since start of treatment period; BG: blood glucose; * (p<.1); ** (p<.5) Source: Lane et al., poster, 87-LB, ADA 216
Slide 8 Tresiba showed lower rate of hypoglycaemia than insulin glargine U1 in maintenance period in the SWITCH 2 trial.8.7.6.5.4.3.2.1 Severe or BG confirmed symptomatic events Cumulative events per patient.9. 16 2 24 28 32 Severe or BG confirmed symptomatic nocturnal events.1.5. 16 2 24 28 32.1.5 Severe events Tresiba glargine U1.3.3 3% * 42% * 46% **.25.25 Lower Lower Lower rate.2 rate.2 rate with with with Tresiba.15 Tresiba.15 Tresiba. 16 2 24 28 32 Weeks 1 Weeks 1 Weeks 1 1 Since start of treatment period; BG: blood glucose; * (p<.1); ** (p=.2127) Source: Wysham et al., poster, 9-LB, ADA 216
Slide 9 Lower hypoglycaemia risk with Tresiba than with insulin glargine U1 in full treatment period in the SWITCH trials SWITCH 1 type 1 diabetes Maintenance period Full treatment period SWITCH 2 type 2 diabetes Rate of severe or BG confirmed symptomatic hypoglycaemia.89 [.85;.94] *.94 [.91;.98] **.7 [.61;.8] *.77 [.7;.85] ** Rate of severe or BG confirmed symptomatic nocturnal hypoglycaemia.64 [.56;.73] *.75 [.68;.83] **.58 [.46;.74] *.75 [.64;.89] ** Rate of severe hypoglycaemia.65 [.48;.89] **.74 [.61;.91] **.54 [.21;1.42] ***.49 [.26;.94] **.25.5 1 2 Favours Tresiba Favours IGlar U1.25.5 1 2 Favours Tresiba Favours IGlar U1 BG: blood glucose; * (p<.1); ** (p<.5); *** (p=.2127); IGlar: insulin glargine Source: Lane et al., poster, 87-LB and Wysham et al., poster, 9-LB, ADA 216
Slide 1 Faster-acting insulin aspart Greater early glucose-lowering effect in type 1 diabetes demonstrated in clinical trials Peter Kurtzhals SVP Global Research
Slide 11 Pooled 1 pharmacological analysis demonstrated faster onset of action with faster-acting insulin aspart in T1D Twice as fast appearance in the bloodstream and twofold insulin exposure within first 3 min IAsp serum faster aspart insulin aspart concentration (pmol/l) 3 n=261 More than 5% greater insulin action within the first 3 minutes GIR (mg/kg/min) 8 faster aspart insulin aspart 25 2 15 n=256 6 4 n=163 n=16 1 5 2 4 9 3 6 Minutes 1 Pooled analysis of PK/PD properties of faster aspart vs insulin aspart included 218 adult subjects with type 1 diabetes from 6 phase 1 randomized, double blind, crossover trials Note: Based on a.2 U/kg dose across all studies for both faster aspart and insulin aspart Source: Heise T et al., poster: 929-P, ADA 216 3 6 Minutes T1D: type 1 diabetes; faster aspart: faster-acting insulin aspart; IAsp: insulin aspart; GIR: glucose infusion rate; n: number randomised patients
Slide 12 Onset 1, a double-blind, treat-to-target trial investigating efficacy and safety of faster-acting insulin aspart in T1D 1,143 people with type 1 diabetes 1 Run-in -8 Onset 1 trial design Faster-acting insulin aspart (mealtime) Faster-acting insulin aspart (post meal) Insulin aspart (mealtime) 26 Weeks 1 Inclusion criteria: Diagnosed with type 1 diabetes at least 12 months prior, age: 18 years or older, basal-bolus insulin treatment for at least 12 months and insulin detemir or insulin glargine treatment for at least 4 months prior to screening, HbA 1C : 7.-9.5%, BMI no higher than 35 Source: Russell-Jones et al., Oral 293-OR, ADA 216 52 Mean age (years) Mean diabetes duration (years) Mean BMI (kg/m 2 ) Baseline characteristics faster aspart (mealtime) insulin aspart (mealtime) faster aspart: faster-acting insulin aspart; BMI: body mass index; FPG: fasting plasma glucose faster aspart (post meal) 46.1 43.7 43.5 2.9 19.3 19.5 26.4 26.7 26.9 Mean HbA 1c 7.6% 7.6% 7.6% Mean FPG (mmol/l) 8.4 7.9 8.1
Slide 13 Greater HbA 1c and PPG reductions with faster aspart dosed at mealtime vs insulin aspart in the onset 1 trial Statistically significantly greater HbA 1c reduction with faster aspart (mealtime) after 26 weeks HbA 1c reduction (%). -.1 -.2 -.3 -.4 -.5 -.6 -.7 * p<.1 faster aspart: faster-acting insulin aspart; PPG: postprandial glucose Source: Russell-Jones et al., Oral 293-OR, ADA 216 faster aspart (post meal) faster aspart (mealtime) insulin aspart (mealtime) -.13 -.17 -.32 * 2 4 6 8 1 12 14 16 18 2 22 24 26 Weeks Lower PPG with faster-acting insulin aspart vs insulin aspart when administered at mealtime PPG increment (mmol/l) 8. 6. 4. 2.. * ** 6 12 18 24 Minutes * p<.1; ** p=.375 faster aspart (mealtime) insulin aspart (mealtime)
Slide 14 Faster-acting insulin aspart appeared to have a safety profile similar to that of insulin aspart in the onset 1 trial Similar rates of treatment-emergent 1 hypoglycaemia across onset 1 treatment arms Severe or BGconfirmed events per subject 3 25 2 15 1 5 faster aspart (post meal) faster aspart (mealtime) insulin aspart (mealtime) Estimated ratio: 1.1 (.88; 1.15) Estimated ratio:.92 (.81; 1.6) 4 8 12 16 2 24 28 Weeks 1 Treatment-emergent was defined as an event that has onset up to 1 day after last day of randomised treatment and excluding the events occurring in the run-in period. Estimated treatment ratios (faster aspart/standard insulin aspart) are presented with 95% confidence intervals BG: blood glucose; faster aspart: faster-acting insulin aspart Source: Russell-Jones et al., Oral 293-OR, ADA 216 Safety conclusions Overall, faster-acting insulin aspart appeared to have a safety profile similar to that of insulin aspart The overall rate of severe or blood glucose-confirmed hypoglycaemia was not statistically significantly different between faster aspart administered at mealtime, administered postmeal and standard insulin aspart administered at mealtime The overall adverse event rates were similar across the three treatment arms There was no difference in antibody development between the three treatment arms
Slide 15 LEADER Statistically significant reduction in risk of major adverse cardiovascular events with Victoza in the LEADER trial Mads Krogsgaard Thomsen EVP and chief science officer
Slide 16 The LEADER trial was designed to investigate the CV profile of Victoza versus placebo in addition to standard of care 9,34 patients with type 2 diabetes LEADER trial design Standard of care + Victoza (.6-1.8 mg once daily) Standard of care + placebo (daily blinded injection) Baseline characteristics Victoza Placebo Mean age (years) 64.2 64.4 Mean diabetes duration (years) 12.8 12.9 Mean BMI (kg/m 2 ) 32.5 32.5 3.5-5. years Key inclusion criteria Adults above 5 years with type 2 diabetes and established cardiovascular disease, or above 6 years with multiple cardiovascular risk factors HbA 1c 7.% CV: cardiovascular Source: Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. The New England journal of medicine. 216; In Press Mean HbA 1c 8.7% 8.7% Systolic BP (mmhg) 135.9 135.9 Diastolic BP (mmhg) 77.2 77. Heart failure * 17.9% 17.8% BP: blood pressure * Heart failure includes New York Heart Association class I, II and III
Slide 17 Victoza statistically significantly reduced the risk of major adverse cardiovascular events in the LEADER trial 13% reduction in 3-point MACE with Victoza compared with placebo Patients with an event (%) 25 2 15 Hazard ratio =.87 95% CI (.78;.97) p<.1 for non-inferiority p=.11 for superiority Superiority of Victoza vs placebo is consistent across sensitivity analyses Victoza Placebo Non-inferiority of Victoza vs placebo was confirmed for time to first MACE Superiority of Victoza vs placebo was confirmed for time to first MACE Victoza reduced the risk by 13% compared to placebo 1 The result was consistent across sensitivity analyses 5 6 12 18 24 3 36 42 48 54 Months MACE: major adverse cardiovascular events; 3-point MACE comprises cardiovascular death, non-fatal myocardial infarction and non-fatal stroke; CI: confidence interval Source: Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. The New England journal of medicine. 216; In Press
Slide 18 All components of 3-point MACE contributed to the reduction in cardiovascular risk in the LEADER trial Patients with an event (%) 1 8 Cardiovascular death HR =.78 95% CI (.66;.94) p=.7 1 8 Non-fatal myocardial infarction HR =.88 95% CI (.75;1.3) p=.11 1 8 Non-fatal stroke Victoza Placebo HR =.89 95% CI (.72;1.11) p=.3 6 6 6 4 4 4 2 2 2 18 36 54 Months HR: hazard ratio; CI: confidence interval Source: Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. The New England journal of medicine. 216; In Press 18 36 54 Months 18 36 54 Months
Slide 19 Victoza also statistically significantly reduced the risk of expanded MACE in the LEADER trial 12% reduction in expanded MACE with Victoza compared with placebo Patients with an event (%) 25 2 15 1 5 Victoza Hazard ratio =.88 95% CI (.81;.96) p=.5 Placebo 6 12 18 24 3 36 42 48 54 Months MACE: major adverse cardiovascular events; Expanded MACE includes cardiovascular death, non-fatal myocadial infarct, non-fatal stroke, coronary revascularization, or hospitalisation for unstable angina pectoris or hospitalisation for heart failure; CI: confidence interval Source: Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. The New England journal of medicine. 216; In Press Numerical reduction in selected secondary cardiovascular outcomes Incidence rate* Victoza Placebo HR Transient ischemic attack 1.3.3.79 Coronary revascularisation Hospitalisation for unstable angina pectoris * Per 1 patient years of observation 1 Not prespecified HR: hazard ratio 2.3 2.5.91.7.7.98 Hospitalisation for heart failure 1.2 1.4.87
Slide 2 Reduced risk of all-cause-death and hospitalisation for heart failure with Victoza vs placebo in the LEADER trial Statistically significant reduction in the rate of death from any cause Patients with an event (%) 14 12 1 8 6 4 2 Months Victoza Placebo HR =.85 95% CI (.74;.97) p=.17 6 12 18 24 3 36 42 48 54 HR: hazard ratio; CI: confidence interval Source: Source: Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. The New England journal of medicine. 216; In Press and Buse et al., Symposium 3-CT-SY24, ADA 216 12 1 8 6 4 2 Numerical reduction in the proportion of patients hospitalised for heart failure Patients with an event (%) 14 6 12 18 24 3 36 42 48 54 Months Victoza Placebo HR =.87 95% CI (.73;1.5) p=.14
Slide 21 Limited HbA 1c difference, but lower severe hypoglycaemia rate and greater weight loss with Victoza in LEADER trial Limited difference in HbA 1c maintained throughout trial HbA 1c (%) 1 ETD: -.4% 95% CI [-.45;-.34] 9 8 7 6 6 12 18 24 3 36 42 48 54 Months 6 5 6 5 5 5 4 5 4 3 5 3 2 5 2 1 5 1 5 Reduction in severe hypoglycaemia Mean episodes per 1 subjects 7 6 5 4 3 2 1 ERR=.68 95% CI (.51;.91) 6 12 18 24 3 36 42 48 4 8 1 2 1 6 2 2 4 2 8 3 2 3 6 4 4 4 4 8 5 2 5 6 6 Months Statistically significantly greater weight loss with Victoza Body weight (Kg) 96 ETD: -2.26 kg 94 95% CI [-2.54;-1.99] ETD: estimated treatment difference, ie estimated mean change from baseline to month 36; ERR: estimated rate ratio Source: Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. The New England journal of medicine. 216; In Press and Buse et al., Symposium 3-CT-SY24, ADA 216 92 9 88 86 Victoza 84 6 12 18 24 3 36 42 48 Months Placebo
Retinopathy Nephropathy ADA 216 investor and analyst event Slide 22 Victoza reduced the risk of microvascular events in the LEADER trial driven by a reduction in nephropathy Patients with an event (%) 1 8 6 4 2 16% reduction in overall microvascular events with Victoza compared to placebo 6 12 18 24 3 36 42 48 54 HR: hazard ratio Source: Buse et al., Symposium 3-CT-SY24, ADA 216 Months Victoza Placebo HR=.84 95% CI (.73;.97) p=.16 Microvascular benefit is driven by 22% reduction in nephropathy Patients with an Victoza Placebo event (%) 1 HR =.78 8 95% CI (.67;.92) 6 p=.3 4 2 6 12 18 24 3 36 42 48 54 1 8 6 4 2 HR = 1.15 95% CI (.87;1.52) p=.33 6 12 18 24 3 36 42 48 54 Months
Slide 23 Victoza appeared to have a safe and well tolerated profile in the LEADER trial Selected adverse events reported during the trial Adverse event Victoza Placebo P-value Acute gallstone disease 3.1% 1.9% <.1 Acute pancreatitis.4%.5%.44 Benign neoplasms 3.6% 3.1%.18 Malignant neoplasms 6.3% 6.%.46 Pancreatic carcinoma.3%.1%.59 Medullary thyroid carcinoma*.%.%.32 Permanent discontinuation due 9.5% 7.3% <.1 to adverse events * One event of medullary thyroid carcinoma occured in the placebo arm, while none occurred in the Victoza arm Source: Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. The New England journal of medicine. 216; In Press GI: gastrointestinal events MedDRA: medical dictionary for regulatory activities Safety conclusions In the LEADER trial, Victoza appeared to have a safe and well tolerated profile, generally consistent with the previous Victoza studies with a higher frequency of adverse events related to GI disorders and acute gallstone disease compared to placebo Pancreatic cancer events in the LEADER trial had the following distribution between the Victoza and placebo arm respectively: - Neoplasm adjudication: 13 vs 5 events - Neoplasm + death adjudication: 13 vs 9 events - MedDRA search in AE database (not adjudicated): 11 vs 1 events
Slide 24 SUSTAIN 2 and 3 Superior HbA 1c and weight reduction with once-weekly injectable semaglutide demonstrated in the SUSTAIN 2 and 3 trials and phase 2 results from oral semaglutide Alan Moses SVP and chief medical officer
Slide 25 Data from all SUSTAIN phase 3a trials for semaglutide to be presented at major conferences in 216 213 214 215 216 SUSTAIN 6: Long-term outcomes trial Min. 14 weeks, n=~3,3 SUSTAIN 1: Monotherapy 3 weeks, n=388 SUSTAIN 2: Semaglutide vs sitagliptin 56 weeks, n=1,231 SUSTAIN 3: Semaglutide vs exenatide once-weekly 56 weeks, n=813 SUSTAIN 4: Semaglutide vs insulin glargine 3 weeks, n=1,89 SUSTAIN 5: Add-on to basal insulin 3 weeks, n=397 Presentation Oral: ENDO 216 Oral: ADA 216 Oral: ADA 216 Poster: AACE 216 Poster: EASD 216 Oral: EASD 216 Note: In the SUSTAIN phase 3a programme,.5 mg and 1. mg doses of semaglutide are being tested in people with type 2 diabetes n: number randomised patients ENDO: Endocrine Society Annual Meeting, April 216; ADA: 76 th Scientific Sessions, American Diabetes Association, June 216; AACE: American Association of Clinical Endocrinologists 25 th Annual Scientific and Clinical Congress, May 216; EASD: 52 nd Annual Meeting of the European Association for the Study of Diabetes, September 216
Slide 26 The SUSTAIN 2 trial compared the safety and efficacy of injectable semaglutide to sitagliptin 1 mg in T2D SUSTAIN 2 trial design Baseline characteristics 1,231 insulinnaïve people with type 2 diabetes 1 Semaglutide.5 mg QW + sitagliptin placebo QD Semaglutide 1. mg QW + sitagliptin placebo QD Sitagliptin 1 mg QD + semaglutide.5 mg placebo QW Mean age (years) Mean diabetes duration (years) Mean BMI (kg/m 2 ) Sema.5 mg Sema 1. mg Sitagliptin 1 mg 54.8 56. 54.6 6.4 6.7 6.6 32.4 32.5 32.5 Sitagliptin 1 mg QD + semaglutide 1. mg placebo QW 56 weeks Mean HbA 1c 8.% 8.% 8.2% Mean FPG (mmol/l) 9.3 9.3 9.6 1 Inclusion criteria: Type 2 diabetes, age: 18 years or older, insulin-naïve on stable diabetes treatment with metformin, thiazolidinediones or metformin + thiazolidinediones 9 days prior to screening, HbA 1c 7.-1.5%. T2D: type 2 diabetes; QW: once weekly; QD: once daily Source: Ahrén, Oral 185-OR, ADA 216 Sema: semaglutide; BMI: body mass index; FPG: fasting plasma glucose
Slide 27 Semaglutide showed superior HbA 1c and weight reduction compared to sitagliptin 1 mg in the SUSTAIN 2 trial Statistically significantly greater reduction in HbA 1c with semaglutide HbA 1c (%) 8.5 8. 7.5 7. 6.5 Semaglutide 1. mg 6.. 8 16 24 32 4 48 56 Weeks Semaglutide.5 mg Sitagliptin 1 mg 7.5 6.8 * 6.5 * -1-2 -3-4 -5-6 -7 Statistically significantly greater weight loss with semaglutide Weight loss (Kg) Semaglutide 1. mg Semaglutide.5 mg Sitagliptin 1 mg 8 16 24 32 4 48 56 Weeks -1.9-4.3 * -6.1 * * p<.1 when comparing semaglutide.5 mg and semaglutide 1. mg to sitagliptin 1 mg Source: Ahrén, Oral 185-OR, ADA 216
Slide 28 The SUSTAIN 3 trial compared the safety and efficacy of injectable semaglutide to exenatide 2. mg in T2D 813 people with type 2 diabetes 1 SUSTAIN 3 trial design Semaglutide 1. mg QW Exenatide 2. mg QW 56 weeks Baseline characteristics Sema 1. mg Exenatide 2. mg Mean age (years) 56.4 56.7 Mean diabetes duration (years) 9. 9.4 Mean BMI (kg/m 2 ) 34. 33.6 Mean HbA 1c 8.4% 8.3% Mean FPG (mmol/l) 1.6 1.4 1 Inclusion criteria: Type 2 diabetes, age: 18 years or older, stable treatment with 1-2 oral antidiabetic drugs (metformin, thiazolidinediones, sulfonylurea), HbA 1c 7.-1.5% T2D: type 2 diabetes; QW: once weekly Source: Ahmann, Oral 187-OR, ADA 216 Sema: semaglutide; BMI: body mass index; FPG: fasting plasma glucose
Slide 29 Semaglutide showed superior HbA 1c and weight reduction versus exenatide once-weekly in the SUSTAIN 3 trial Statistically significantly greater reduction in HbA 1c with semaglutide HbA 1c (%) 8.5 8. 7.5 7. 6.5 Semaglutide 1. mg Exenatide 2. mg 6.. 8 16 24 32 4 48 56 Weeks 7.4 6.8 * Weight loss (kg) -1-2 -3-4 -5-6 -7 Statistically significantly greater weight loss with semaglutide Semaglutide 1. mg 8 16 24 32 4 48 56 Weeks Exenatide 2. mg -1.9-5.6 * * p-value <.1 Source: Ahmann, Oral 187-OR, ADA 216
Slide 3 Semaglutide appeared to have a safe and well tolerated profile in the SUSTAIN 2 and 3 trials Rates of nausea with semaglutide in SUSTAIN 2 and 3 trials Semaglutide 1. mg Semaglutide.5 mg Sitagliptin 1 mg Exenatide 2. mg Subjects experiencing nausea 2% 15% SUSTAIN 2 1% 5% % 6 12 18 24 3 36 42 48 54 6 2% 15% 1% 5% % 6 12 18 24 3 36 42 48 54 6 Weeks GLP-1: glucagon-like peptide-1 Source: Ahrén, Oral 185-OR and Ahmann, Oral 187-OR, ADA 216 SUSTAIN 3 GLP-1-related run-in side effects reduced through selected titration scheme in trials Generally, semaglutide appeared to have a safe and welltolerated profile in the SUSTAIN 2 and 3 trials While semaglutide caused more GI adverse events than sitagliptin and exenatide, GI disorders were similar to those reported with other GLP-1s Discontinuation rates due to adverse events for semaglutide were low indicating that regular GLP-1-related run-in side effects have been reduced through the selected titration scheme GI: gastrointestinal
Slide 31 Oral semaglutide in five daily doses compared with injectable semaglutide and placebo in phase 2 trial Phase 2 trial design 1,2 Baseline characteristics Oral sema QD 2.5 mg Oral sema Placebo sc sema 632 people with type 2 diabetes 3 Oral sema QD Oral sema QD Oral sema QD Oral sema QD Placebo QD sc sema QW 2.5 5 1 2.25.5 Weeks 4 8 12 1 Semaglutide sc arm was open-label, whereas all tablet arms were double-blind 2 Dosing conditions: Tablets administered in the fasting state, subjects abstained from food and fluid intake for at least 3 minutes after tablet ingestion 3 Inclusion criteria: type 2 diabetes, age: 18 years or older, BMI higher than 25 and lower than 4 kg/m 2, treated with diet and exercise with or without metformin, HbA 1c : 7.-9.5% sc: subcutaneous; QW: once weekly; QD: once daily 5 5 5 mg 1 mg 1 Placebo 2 mg 1. mg 4 mg 26 Mean age (years) Mean diabetes duration (years) Sema: semaglutide Source: Rosenstock et al., OR15-3, ENDO 216 55.7-58.3 58.9 56.8 7.8-8.1 6.7 5.6 Body weight (kg) 9.9-93.8 93.8 88.8 Mean BMI (kg/m 2 ) 31.1-32. 32.6 3.7 Mean HbA 1c 7.8-8.1% 8.% 7.8% Treated with metformin 84-87% 82% 84%
Slide 32 Oral semaglutide dose dependently reduced HbA 1c and body weight in phase 2 trial HbA 1c reduction from a mean baseline of 7.9% HbA 1c (%) 8. Weight loss from a mean base line of 92 kg Placebo Sema 2.5 mg Sema 5 mg Sema 1 mg Sema 2 mg Sema 4 mg Sema 1 mg sc Weight loss (kg) 7.5-2 7. 6.5-4 6. -6 5.5. 2 4 6 8 1 12 14 16 18 2 22 24 26 Weeks -8 2 4 6 8 1 12 14 16 18 2 22 24 26 Weeks Inclusion criteria: Type 2 diabetes, 7.% HbA 1c 9.5%, treatment with diet and exercise with or without metformin; sc: subcutaneous; sema: semaglutide Dotted line indicates the target for HbA 1c of 7.% as recommended by the American Diabetes Association Source: Rosenstock et al., OR15-3, ENDO 216
Slide 33 The safety and tolerability profile of oral semaglutide was similar to injectable semaglutide in phase 2 clinical trial GI adverse events with oral semaglutide were comparable to injectable semaglutide Proportion of subjects 5% 4% 3% 2% 1% Placebo Sema 2.5 mg Sema 5 mg Sema 1 mg Sema 2 mg Sema 4 mg Sema 1 mg sc Safety conclusions Overall, oral semaglutide appeared to have a safe and well-tolerated profile in the trial GI adverse events with oral semaglutide were similar to injectable semaglutide Dose-dependent increase in discontinuation rates observed in the trial Only few events of pancreatitis, gallbladder disorders or malignant neoplasms were observed in the trial % Nausea Vomiting Diarrhea GI: gastrointestinal; sc: subcutaneous Source: Rosenstock et al., OR15-3, ENDO 216
Slide 34 Concluding remarks Steady Tresiba growth in the US. In Japan Tresiba market share continues to grow despite biosimilar launch Tresiba demonstrated lower rates of hypoglycaemia than insulin glargine U1 in the SWITCH trials Early onset of faster-acting insulin aspart leads to improved HbA 1c and PPG versus insulin aspart in onset 1 trial Victoza demonstrated statistically significant 13% reduction in MACE and reduced cardiovascular and all cause mortality statistically significantly by 22% and 15 %, respectively, compared to placebo in the LEADER trial Semaglutide QW demonstrated superior HbA 1c and body weight reductions against comparators in SUSTAIN 2 and 3 Oral semaglutide dose dependently reduced HbA 1c and body weight in a 26-week phase 2 trial in type 2 diabetes PPG: postprandial plasma glucose; MACE: major adverse cardiovascular events; QW: once weekly
Slide 35 Q&A session Jakob Riis, EVP China, Pacific and Marketing Mads Krogsgaard Thomsen, EVP and CSO Peter Kurtzhals, SVP Global Research Peter Kristensen, SVP Global Development Alan Moses, SVP and CMO
Slide 36 Investor contact information Share information Novo Nordisk s B shares are listed on the stock exchange in Copenhagen under the symbol NOVO B. Its ADRs are listed on the New York Stock Exchange under the symbol NVO. For further company information, visit Novo Nordisk on the internet at: novonordisk.com Upcoming events 5 Aug 216 Financial statement for the first six months of 216 28 Oct 216 Financial statement for the first nine months of 216 2 Feb 217 Financial statement for 216 Investor Relations contacts Novo Nordisk A/S Investor Relations Novo Allé, DK-288 Bagsværd Peter Hugreffe Ankersen +45 375 985 phak@novonordisk.com Melanie Raouzeos +45 375 3479 mrz@novonordisk.com In North America: Kasper Veje +1 69 235 8567 kpvj@novonordisk.com
Slide 37 Appendix Glossary Abbreviation Meaning Abbreviation Meaning Abbreviation Meaning AACE American Association of Clinical Endocrinologists FPG Fasting plasma glucose MS Market share ADA American Diabetes Association GIR Glucose infusion rate NS Not statistically significant BG Blood glucose GLP-1 Glucagon-like peptide-1 OAD Oral anti-diabetic agent BMI Body mass index (kg/m 2 ) HbA 1c Glycated haemoglobin A 1c PPG Postprandial glucose BP Blood pressure HR Hazard ratio QD Once daily CI Confidence interval IAsp Insulin aspart QW Once weekly CV Cardiovascular IDeg Insulin degludec SC Subcutaneous EASD European Association for the Study of Diabetes ENDO Endocrine Society MACE ETD Estimated treatment difference MedDRA IGlar Insulin glargine Sema Semaglutide Major adverse cardiovascular event Medical dictionary for regulatory activities T1D/T2D TRx Type 1 diabetes/type 2 diabetes Total prescriptions