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Presenter Disclosure Information

Presenter Disclosure Information. The American Diabetes Association requires the following disclosure to the participants: Alan Garber, MD, PhD, FACE.

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Presenter Disclosure Information

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  1. Presenter Disclosure Information The American Diabetes Association requires the following disclosure to the participants: Alan Garber, MD, PhD, FACE Research Support (payable to Baylor College of Medicine) from:Novo Nordisk A/SBristol-Myers SquibbGlaxo Smith-KlineRoche Sanofi-AventisMerck & Co.Daiichi Sankyo Advisor and Speaker for:Novo Nordisk A/SMerck & Co.Glaxo Smith-KlineRocheDaiichi Sankyo

  2. Insulin Degludec Improves Long-term Glycemic Control with Less Nocturnal Hypoglycemia Compared with Insulin Glargine:1-year Results from a Randomized Basal-bolus Trial in People with Type 2 Diabetes(BEGIN™: BB T2)Alan Garber*, Allen King, Ann Marie Ocampo Francisco, Lars Endahl, and Priscilla Hollander Clinicaltrials.gov identifier: NCT00972283 *Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Baylor College of Medicine, Houston, TX

  3. Study design IDeg OD* + IAsp± metformin ± pioglitazone (n=755) Patients with advanced type 2 diabetes (n=1006) IGlar OD§+ IAsp ± metformin ± pioglitazone (n=251) • Inclusion criteria • Type 2 diabetes ≥6 months • Previously treated with any • insulin regimen ≥3 months • ± OADs • HbA1c 7–10% • BMI ≤ 40 kg/m2 • Age ≥ 18 years 0 52 weeks Randomized 3:1 Open label *Dosed with eveningmeal § Dosed any time of day but same time every day (as per label) IAsp, insulin aspart; IDeg, insulin degludec; IGlar, insulin glargine;

  4. Titration algorithm: IDeg and IGlar a Mean of 3 consecutive days’ measurementsb Unless there is obvious explanation for the low value, such as a missed meal

  5. Subject disposition 1440 Screened 434Failed screening criteria 1006 Randomized 251Randomized to IGlar OD + IAsp 755Randomized to IDeg OD + IAsp Withdrawals: 137 (18%) Adverse event: 31 (4%) Non-compliance: 23 (3%) Ineffective therapy: 3 (0.4%) Other: 80 (11%) Withdrawals: 40 (16%) Adverse event: 9 (4%) Non-compliance: 12 (5%) Ineffective therapy: 0 Other: 19 (8%) 618 (82%)Completers 211 (84%)Completers 3:1 randomization

  6. Baseline characteristics Values are mean (±SD)

  7. HbA1c over time IDeg OD + IAsp (n=744) IGlar OD + IAsp (n=248) Treatment difference: Non-inferior 0 Full Analysis Set; LOCF Comparisons: Estimates adjusted for multiple covariates

  8. Fasting plasma glucose over time IDeg OD + IAsp (n=744) IGlar OD + IAsp (n=248) Treatment difference: –5.22, ns 0 Full Analysis Set; LOCF Comparisons: Estimates adjusted for multiple covariates

  9. Prandial increment IDeg OD + IAsp (n=744) IGlar OD + IAsp (n=248) ns ns ns ns Full Analysis Set; LOCF Comparisons: Estimates adjusted for multiple covariates

  10. Daily insulin doses Safety Analysis Set; LOCF

  11. Hypoglycemia classification Suspected hypoglycemia or routine PG measurement Patient able to treat self? Yes No PG <56 mg/dL* No Yes Not classified as trial hypoglycemia Confirmed hypoglycemia Severe hypoglycemia Minor hypoglycemia *: With or without symptoms A nocturnal episode is any confirmed episode with time of onset between 12:01 and 05.59 am

  12. Confirmed hypoglycemia IDeg OD + IAsp (n=753) IGlar OD + IAsp (n=251) 18% risk reduction p=0.036 Safety Analysis Set; PYE: patient-years of exposure Comparisons: Estimates adjusted for multiple covariates

  13. Nocturnal hypoglycemia IDeg OD + IAsp (n=753) IGlar OD + IAsp (n=251) 200 180 25% risk reduction p=0.040 160 140 120 Confirmed nocturnal hypoglycemia (cumulative events per 100 PYE) 100 80 60 40 20 0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Time (weeks) Safety Analysis Set; PYE: patient-years of exposure Comparisons: Estimates adjusted for multiple covariates A nocturnal episode is any confirmed episode with time of onset between 00:01 and 05.59am

  14. Hypoglycemia summary *RR:0.82, p=0.036**RR: 0.75, p=0.040 Safety Analysis Set; n: number of patients; %: proportion of patients; rate: Number of events per patient yearRR: relative risk for IDeg OD/IGlar OD

  15. Quality of lifeSF-36 physical and mental scores Favors glargine Favors degludec Overall physical Physical functioning Physical scores Role physical * Bodily pain General health Overall mental Vitality Mental scores Social functioning Role emotional Mental health -1 0 1 2 Treatment difference (IDeg-IGlar) Full Analysis Set; LOCF Comparisons: Estimates adjusted for multiple covariates *significantly better

  16. Adverse events Only treatment-emergent events occurring after first exposure and before 7 days after last exposure PYE: Patient-years of exposure SAE: serious adverse event

  17. Conclusions Using a titration control algorithm (treat to target): • Insulin degludec produced the same glycemic control as insulin glargine • Insulin degludec produced less hypoglycemia • 18% less risk of overall confirmed hypoglycemia • 25% less risk of nocturnal hypoglycemia • Insulin degludec improved quality of life • Insulin degludec was safe and well tolerated for 1 year

  18. Hypoglycemia results consistent with BEGIN™ pre-specified meta-analyses 26%* T1 and T2 36%* T2 basal only 9%* T1 and T2 17%* T2 basal only Nocturnal hypoglycemia Reduction in confirmed hypoglycemia withdegludec(all degludec vs glargine studies) (all degludec vs glargine studies, T1 and T2) Trial (wks) BEGIN™ BB T1 (52) Nocturnal BEGIN™ Flex T1 (26) BEGIN™ BB T2 (52) BEGIN™ Once Long (52) BEGIN™ Low Vol (26) Overall BEGIN™ Once Asia (26) BEGIN™ Flex T2 (26) 26% risk reduction Meta-analysis 0.0 0.5 1.0 1.5 2.0 *: Statistically significant improvement Favors degludec Favorsglargine The meta-analyses were pre-specified as part of the BEGIN™ phase 3a trials for insulin degludec Reference: http://www.novonordisk.com/images/investors/investor_presentations/2011/CMD2011/04_Diabetes_treatment_tomorrow_CMD2011.pdf

  19. Acknowledgements All participants All principal investigators Bulgaria Mihail Protich Valentin Ivanov Natalia Veleva Mariyana Pichmanova Joulieta Guerenova Kiril Hristozov Antoanela Slavcheva Petrova-Gancheva Zhulieta Prakova-Teneva Germany Michael Böhmer Hans-Ulrich Clever Marcel Kaiser Hans Peter-Kempe Andrea Mölle Rainer Paulus Ludger Rose Joachim Sauter Ireland Brendan Kinsley John Nolan Seamus Sreenan Frances Hayes South Africa Pankaj Joshi Duma Tseliso Khutsoane Jeevren Reddy Leila Mayet Lesley Jean Burgess Spain Pedro Mezquita Raya Mercedes Rigla Cros Alfonso Calle Sergio Donnay Candil Alfonso Soto Juan Francisco Merino Torres Jose Ramón Dominguez Jordi Mesa Angel Luis Marco Mur Italy Stefano Del Prato Sebastiano Filetti PierMarco Piatti Giacomo Vespasiani Fausto Santeusanio & Carmine Giuseppe Fanelli Edoardo Mannucci Agostino Consoli Pietro Pata Mauro Cignarelli Vito Borzì Roberto Trevisan Romania Viorel Serban Doina Catrinoiu Gabriela Creteanu Lavinia Pop Anca Coman Russia Sergey Dogadin Irina Dvoryashina Irina Karpova Tatyana Lysenko Elena Smirnova Vladimir Yakusevich Slovakia Jaroslav Fábry Adriana Ilavská Lívia Tomášová Eva Tošerová Hong Kong Francis CC Chow Turkey Kubilay Karsidag Mecdi Erguney Esen Akaby Mustafa Kemal Balçi United States Corey Anderson Claire Baker Recardo Berbano Thomas Blevins Vasti Broadstone Michael Brody John Brunner (USA cont.) Osvaldo Brusco Christopher Case Richard Cherlin Leonard Chuck James Clower Gordon Conner Michael Cooperman Alan Paysinger Michael Early Steven Elliott David Fitz-Patrick Keving Furlong Alan Garber Linda Glaser Stewart Albert George Griffing Lane Handke Ronald Harris Kathie Hermayer Priscilla Hollander Richard Huntley William Kaye John Kennedy Allen King Eric Klein Robert Lipitz Phillip Snell Emily Morawski Ruth Nurnberg Robert Orr (USA cont.) Kwame Osei Eileen Palace George Raad Brian Rasmussen Michael Reeves Victor Roberts Helena Rodbard Paul Rosenblit Julio Rosenstock Jean-Louis Selam Stephanie Shaw John Shelmut Henry Simon Muhammed Smith Stanley Stringam Allen Sussman John Testa Angela Mazza Susann Varano Mark Warren Peter Winkle Jonathan Wise Vanita Aroda Robert Strzinek Milton Wong Jeffrey Pollock Bruce Bode

  20. Back-up slides

  21. 16% Overall 14% 12% 10% 8% 6% 4% 2% 0% 1 4 7 10 13 16 19 22 25 28 31 34 37 40 50% Nocturnal 40% 30% Percentage of subjects 20% 10% 0% 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Confirmed hypoglycemic episodes IDeg OD + IAsp (n=753) IGlar OD + IAsp (n=251) Percentage of subjects Number of hypoglycemic episodes

  22. Weight change Treatment difference: –0.68 [–2.16; 0.82] Change in weight from baseline (lb) IDeg OD + IAsp (n=753) IGlar OD + IAsp (n=251) Baseline 204.2 lb 203.3 lb Safety Analysis Set; LOCF; Comparisons: Estimates adjusted for multiple covariates

  23. Participating countries Slovakia 4% Germany 6% Russia 4% United States 50% Romania3% Ireland3% Bulgaria8% Spain7% Italy6% Hong Kong2% Turkey1% South Africa5%

  24. Titration algorithm: IDeg and IGlar aMean of 3 consecutive days’ measurementsbUnless there is obvious explanation for the low value, such as a missed meal

  25. Titration algorithm: IAsp Titration of IAsp should only occur after the first 8 weeks of the study *Mean of 3 consecutive days’ measurements

  26. Daily insulin doses Safety Analysis Set; LOCF

  27. AEs occurring with a frequency >5% by SOC and PT n, number of patients; %, proportion of patients; E, number of eventsR, number of events per 100 patient-years SOC: System Organ Class; PT, Preferred term

  28. SAEs possibly/probably related to the trial product by SOC and PT n, number of patients; %, proportion of patients; E, number of eventsR, number of events per 100 patient-years SOC: System Organ Class; PT, Preferred term

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