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Tirzepatide is a novel dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist under development for the treatment of type 2 diabetes. In this study, we used continuous glucose monitoring (CGM) to compare the 24 h glucose profile for participants given tirzepatide compared with those given insulin degludec.This substudy of the open-label, parallel-group, phase 3 SURPASS-3 trial, was done at 45 sites across six countries (Hungary, Poland, Romania, Spain, Ukraine, and the USA). Eligible participants in the main study were adults with type 2 diabetes, a baseline HbAFrom April 1 to Nov 27, 2019, 313 participants were screened for eligibility, 243 of whom were enrolled in CGM substudy (tirzepatide 5 mg, n=64; tirzepatide 10 mg, n=51; tirzepatide 15 mg, n=73; and insulin degludec, n=55). Patients given once-weekly tirzepatide (pooled 10 mg and 15 mg groups) had a greater proportion of time in tight target range compared with patients given insulin degludec (estimated treatment difference 25% [95% CI 16-33]; p0·0001). Participants assigned to tirzepatide spent significantly more time in tight target range at 52 weeks compared with those assigned to insulin degludec (5 mg 12% [1-22], p=0·031; 10 mg 24% [13-35], p0·0001; and 15 mg 25% [14-35], p0·0001). Participants assigned to tirzepatide 10 mg and 15 mg, but not to tirzepatide 5 mg, spent significantly more time in tight target range at 24 weeks compared with insulin degludec (10 mg 19% [8-30], p=0·0008; 15 mg 21% [11-31], p0·0001).Once-weekly treatment with tirzepatide showed superior glycaemic control measured using CGM compared with insulin degludec in participants with type 2 diabetes on metformin, with or without a SGLT2 inhibitor. These new data provide additional evidence to the effect of tirzepatide and potential for achieving glycaemic targets without increase of hypoglycaemic risk compared with a basal insulin.Eli Lilly and Company.

We assessed current understandings in interpretation of Bayesian and traditional statistical results within the clinical researcher (non-statistician) community.Within a 22-question survey, including demographics and experience and comfort levels with Bayesian analyses, we included questions on how to interpret both Bayesian and traditional statistical outputs. We also assessed whether Bayesian or traditional interpretations are considered more useful.Among the 323 respondent clinicians, 42.4% and 36.5% chose the correct interpretations of the posterior probability and 95% credible interval, respectively. Only 11.5% of respondents interpreted the p-value correctly and 23.5% interpreted the 95% confidence interval correctly.Based on these survey results, we conclude that most of these clinicians face uncertainty when attempting to interpret results from both Bayesian and traditional statistical outputs. When presented with accurate interpretations, clinicians generally conclude that Bayesian results are more useful than conventional ones. We believe there is a need for education of clinicians in statistical interpretation in ways that are customized to this audience.

Tirzepatide (TZP) is a novel dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist in development for T2D. In a continuous glucose monitoring (CGM) sub-study of SURPASS-3 (NCT03882970) , participants with T2D on metformin with or without SGLT-2 inhibitors spent up to 91% of time in range (71-180 mg/dL) for TZP (5, 10, 15 mg) vs. 75% for insulin degludec (IDeg) (p Disclosure R.M.Bergenstal: Advisory Panel; Hygieia, Medtronic, Roche Diabetes Care, Zealand Pharma A/S, Consultant; Abbott Diabetes, Ascensia Diabetes Care, Bigfoot Biomedical, Inc., CeQur SA, Dexcom, Inc., Eli Lilly and Company, Novo Nordisk, Onduo LLC, Sanofi, United HealthCare Services, Inc., Research Support; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk, Sanofi. A.Bartee: None. M.Zeytinoglu: Employee; Eli Lilly and Company. R.Bray: Employee; Eli Lilly and Company. S.Allen: None. K.Brown: Employee; Eli Lilly and Company.

Context Novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (RA) tirzepatide demonstrated substantially greater glucose control and weight loss (WL) compared with selective GLP-1RA dulaglutide. Objective Explore mechanisms of glucose control by tirzepatide. Design Post hoc analyses of fasting biomarkers and multiple linear regression analysis. Setting Forty-seven sites in 4 countries. Patients or other Participants Three hundred and sixteen subjects with type 2 diabetes. Interventions Tirzepatide (1, 5, 10, 15 mg), dulaglutide (1.5 mg), placebo. Main Outcome Measures Analyze biomarkers of beta-cell function and insulin resistance (IR) and evaluate WL contributions to IR improvements at 26 weeks. Results Homeostatic model assessment (HOMA) 2-B significantly increased with dulaglutide and tirzepatide 5, 10, and 15 mg compared with placebo (P ≤ .02). Proinsulin/insulin and proinsulin/C-peptide ratios significantly decreased with tirzepatide 10 and 15 mg compared with placebo and dulaglutide (P ≤ .007). Tirzepatide 10 and 15 mg significantly decreased fasting insulin (P ≤ .033) and tirzepatide 10 mg significantly decreased HOMA2-IR (P = .004) compared with placebo and dulaglutide. Markers of improved insulin sensitivity (IS) adiponectin, IGFBP-1, and IGFBP-2 significantly increased by 1 or more doses of tirzepatide (P < .05). To determine whether improvements in IR were directly attributable to WL, multiple linear regression analysis with potential confounding variables age, sex, metformin, triglycerides, and glycated hemoglobin A1c was conducted. WL significantly (P ≤ .028) explained only 13% and 21% of improvement in HOMA2-IR with tirzepatide 10 and 15 mg, respectively. Conclusions Tirzepatide improved markers of IS and beta-cell function to a greater extent than dulaglutide. IS effects of tirzepatide were only partly attributable to WL, suggesting dual receptor agonism confers distinct mechanisms of glycemic control.

Aim To assess the efficacy and tolerability of tirzepatide treatment using three different dose‐escalation regimens in patients with type 2 diabetes. Materials and Methods In this double‐blind, placebo‐controlled study, patients were randomized (1:1:1:1) to receive either once‐weekly subcutaneous tirzepatide or placebo. The tirzepatide dose groups and dose‐escalation regimens were: 12 mg (4 mg weeks 0–3; 8 mg weeks 4–7; 12 mg weeks 8–11), 15 mg‐1 (2.5 mg weeks 0–1; 5 mg weeks 2–3; 10 mg weeks 4–7; 15 mg weeks 8–11) and 15 mg‐2 (2.5 mg weeks 0–3; 7.5 mg weeks 4–7; 15 mg weeks 8–11). The primary objective was to compare tirzepatide with placebo in HbA1c change from baseline at 12 weeks. Results Overall, 111 patients were randomized: placebo, 26; tirzepatide 12 mg, 29; tirzepatide 15 mg‐1, 28; tirzepatide 15 mg‐2, 28. The mean age was 57.4 years, HbA1c 8.4% and body mass index 31.9 kg/m2. At week 12, absolute HbA1c change from baseline (SE) was greater in the tirzepatide treatment groups compared with placebo (placebo, +0.2% [0.21]; 12 mg, −1.7% [0.19]; 15 mg‐1, −2.0% [0.20]; 15 mg‐2, −1.8% [0.19]). The incidence of nausea was: placebo, 7.7%; 12 mg group, 24.1%; 15 mg‐1 group, 39.3%; 15 mg‐2 group, 35.7%. Three patients discontinued the treatment because of adverse events, one from each of the placebo, 12 mg and 15 mg‐1 groups. Conclusions Tirzepatide treatment for 12 weeks resulted in clinically significant reductions in HbA1c. This suggests that lower starting doses and smaller dose increments are associated with a more favourable side effect profile.

Tirzepatide is a novel dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist under development for the treatment of type 2 diabetes. We aimed to assess the efficacy and safety of tirzepatide versus titrated insulin degludec in people with type 2 diabetes inadequately controlled by metformin with or without SGLT2 inhibitors. Methods: In this open-label, parallel-group, multicentre (122 sites), multinational (13 countries), phase 3 study, eligible participants (aged ≥18 years) had a baseline glycated haemoglobin (HbA1c) of 7·0-10·5%, body-mass index of at least 25 kg/m2, stable weight, and were insulin-naive and treated with metformin alone or in combination with an SGLT2 inhibitor for at least 3 months before screening. Participants were randomly assigned (1:1:1:1), using an interactive web-response system, to once-weekly subcutaneous injection of tirzepatide (5, 10, or 15 mg) or once-daily subcutaneous injection of titrated insulin degludec, and were stratified by country, HbA1c, and concomitant use of oral antihyperglycaemic medications. Tirzepatide was initially given at 2·5 mg and the dose was escalated by 2·5 mg every 4 weeks until the assigned dose was reached. Insulin degludec was initially given at 10 U per day and was titrated once weekly to a fasting self-monitored blood glucose of less than 5·0 mmol/L (

Tirzepatide (TZP) is a novel dual GIP/GLP-1 receptor agonist under development for the treatment of type 2 diabetes (T2D). The efficacy and safety of TZP vs. titrated insulin degludec (IDeg) were assessed in insulin-naive patients with T2D inadequately controlled on metformin with/without SGLT-2i. In this open-label, 52-week, Phase 3 study, 1444 patients with T2D were randomized (1:1:1:1) to once-weekly TZP (5, 10, 15 mg) or once-daily IDeg (mean baseline [BL] age, 57.4 years; T2D duration, 8.4 years; HbA1c, 8.17%; BMI, 33.5 kg/m2; 32% on SGLT-2i). The primary efficacy endpoint was mean change in HbA1c from BL to Week 52. Secondary efficacy endpoints included mean change in fasting serum glucose (FSG) and body weight (BW) and proportion of subjects achieving HbA1c and BW goals. All TZP doses were superior to IDeg in mean change from BL in HbA1c and BW, and in the proportion of patients achieving all HbA1c and BW goals at Week 52 (Table). Among patients taking TZP 15 mg, 48.4% achieved HbA1c Disclosure B. Ludvik: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Research Support; Self; Amgen Inc., Eli Lilly and Company, Novo Nordisk, Speaker’s Bureau; Self; MSD Corporation. F. Giorgino: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Novo Nordisk, Roche Diabetes Care, Sanofi, Research Support; Self; Lilly Diabetes, Roche Diabetes Care. E. Jodar: Other Relationship; Self; AstraZeneca, Lilly Diabetes, Mundipharma International, Novo Nordisk, Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH. J. Frias: Consultant; Self; 89bio, Inc., Altimmune, Axcella Health Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk, Pfizer Inc., Sanofi, Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, CymaBay Therapeutics, Eli Lilly and Company, Intercept Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc., Sanofi, Speaker’s Bureau; Self; Merck & Co., Inc., Sanofi. L. Fernandez lando: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. K. Brown: Employee; Self; Eli Lilly and Company. R. Bray: None. A. Rodriguez: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. Funding Eli Lilly and Company

LY3305677 (LY) is an acylated single chain peptide analog of mammalian oxyntomodulin designed for once weekly dosing. It has dual pharmacology of GLP-1 and glucagon and has therapeutic potential for T2D, obesity and NASH. This randomized, double blind, placebo-controlled phase 1 study assessed safety and tolerability of single ascending doses of LY. Healthy subjects (N=48) were randomized (6:2) and 47 received subcutaneous LY (6 doses: 0.03 mg to 5.0 mg) or placebo. Safety biomarkers, LY pharmacokinetics (PK), and key exploratory pharmacodynamic (PD) biomarkers were assessed including fasting insulin, glucagon, triglyceride levels, and body weight. Most common LY-related AEs were gastrointestinal events. Dose-dependent increase in nausea, decreased appetite, and vomiting were seen. Most of the events were mild and transient. Increase in heart rate was noted, which returned to baseline for most groups at follow-up visit. No injection site reactions were seen. Median time to maximum LY concentration ranged from 18.2 to 72.1 h, and geometric mean half-life ranged from 7.5 to 9.8 days. Generally, mean fasting insulin level increased within 24 h and lasted over 8 days. At Day 8, LY 2.5 mg and 5.0 mg reduced mean fasting glucagon levels by 2.33 pmol/L and 2.67 pmol/L, respectively as compared with placebo. At Day 5, mean fasting triglyceride levels reduced from baseline by 0.5 mmol/L with LY 5.0 mg as compared to 0.1 mmol/L with placebo. Change from baseline in body weight reached a maximum -2.4 kg with the 5 mg dose, versus -0.5 kg for placebo at Day 8 and this effect was sustained through Day 29 at 5 mg. LY3305677 PK properties are suitable for once-weekly dosing with a safety and tolerability profile similar to other incretins in Phase 1 trials, supporting future clinical evaluation. Disclosure L. Tham: Employee; Self; Eli Lilly and Company. M. K. Thomas: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. C. Benson: Employee; Self; Eli Lilly and Company. R. Bray: None. C. Tang: Employee; Self; Eli Lilly and Company, Employee; Spouse/Partner; Novartis AG. C. Loghin: Employee; Self; Eli Lilly and Company. Funding Eli Lilly and Company

Objective: To determine the effect of tirzepatide, a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, on biomarkers of nonalcoholic steatohepatitis (NASH) and fibrosis in T2DM patients. Research Design and Methods: T2DM patients received either once weekly tirzepatide (1, 5, 10, or 15 mg), dulaglutide (1.5 mg), or placebo for 26 weeks. Changes from baseline in alanine aminotransferase (ALT), aspartate aminotransferase (AST), Keratin-18 (K-18), Procollagen III (Pro-C3), and adiponectin, were analyzed in a modified intent-to-treat population. Results: Significant (p Conclusions: In post-hoc analyses, higher tirzepatide doses significantly decreased NASH-related biomarkers and increased adiponectin in T2DM patients.

The effects of tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, as an addition to insulin glargine for treatment of type 2 diabetes have not been described.To assess the efficacy and safety of tirzepatide added to insulin glargine in patients with type 2 diabetes with inadequate glycemic control.Randomized phase 3 clinical trial conducted at 45 medical research centers and hospitals in 8 countries (enrollment from August 30, 2019, to March 20, 2020; follow-up completed January 13, 2021) in 475 adults with type 2 diabetes and inadequate glycemic control while treated with once-daily insulin glargine with or without metformin.Patients were randomized in a 1:1:1:1 ratio to receive once-weekly subcutaneous injections of 5-mg (n = 116), 10-mg (n = 119), or 15-mg (n = 120) tirzepatide or volume-matched placebo (n = 120) over 40 weeks. Tirzepatide was initiated at 2.5 mg/week and escalated by 2.5 mg every 4 weeks until the assigned dose was achieved.The primary end point was mean change from baseline in glycated hemoglobin A1c (HbA1c) at week 40. The 5 key secondary end points included mean change in body weight and percentage of patients achieving prespecified HbA1c levels.Among 475 randomized participants (211 [44%] women; mean [SD] age, 60.6 [9.9] years; mean [SD] HbA1c, 8.31% [0.85%]), 451 (94.9%) completed the trial. Treatment was prematurely discontinued by 10% of participants in the 5-mg tirzepatide group, 12% in the 10-mg tirzepatide group, 18% in the 15-mg tirzepatide group, and 3% in the placebo group. At week 40, mean HbA1c change from baseline was -2.40% with 10-mg tirzepatide and -2.34% with 15-mg tirzepatide vs -0.86% with placebo (10 mg: difference vs placebo, -1.53% [97.5% CI, -1.80% to -1.27%]; 15 mg: difference vs placebo, -1.47% [97.5% CI, -1.75% to -1.20%]; P .001 for both). Mean HbA1c change from baseline was -2.11% with 5-mg tirzepatide (difference vs placebo, -1.24% [95% CI, -1.48% to -1.01%]; P .001]). Mean body weight change from baseline was -5.4 kg with 5-mg tirzepatide, -7.5 kg with 10-mg tirzepatide, -8.8 kg with 15-mg tirzepatide and 1.6 kg with placebo (5 mg: difference, -7.1 kg [95% CI, -8.7 to -5.4]; 10 mg: difference, -9.1 kg [95% CI, -10.7 to -7.5]; 15 mg: difference, -10.5 kg [95% CI, -12.1 to -8.8]; P .001 for all). Higher percentages of patients treated with tirzepatide vs those treated with placebo had HbA1c less than 7% (85%-90% vs 34%; P .001 for all). The most common treatment-emergent adverse events in the tirzepatide groups vs placebo group were diarrhea (12%-21% vs 10%) and nausea (13%-18% vs 3%).Among patients with type 2 diabetes and inadequate glycemic control despite treatment with insulin glargine, the addition of subcutaneous tirzepatide, compared with placebo, to titrated insulin glargine resulted in statistically significant improvements in glycemic control after 40 weeks.ClinicalTrials.gov Identifier: NCT04039503.

OBJECTIVE To determine the effect of tirzepatide, a dual agonist of glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptors, on biomarkers of nonalcoholic steatohepatitis (NASH) and fibrosis in patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS Patients with T2DM received either once weekly tirzepatide (1, 5, 10, or 15 mg), dulaglutide (1.5 mg), or placebo for 26 weeks. Changes from baseline in alanine aminotransferase (ALT), aspartate aminotransferase (AST), keratin-18 (K-18), procollagen III (Pro-C3), and adiponectin were analyzed in a modified intention-to-treat population. RESULTS Significant (P < 0.05) reductions from baseline in ALT (all groups), AST (all groups except tirzepatide 10 mg), K-18 (tirzepatide 5, 10, 15 mg), and Pro-C3 (tirzepatide 15 mg) were observed at 26 weeks. Decreases with tirzepatide were significant compared with placebo for K-18 (10 mg) and Pro-C3 (15 mg) and with dulaglutide for ALT (10, 15 mg). Adiponectin significantly increased from baseline with tirzepatide compared with placebo (10, 15 mg). CONCLUSIONS In post hoc analyses, higher tirzepatide doses significantly decreased NASH-related biomarkers and increased adiponectin in patients with T2DM.

Nonalcoholic fatty liver disease (NAFLD) is common in T2D patients and increases the risk of NASH and cirrhosis. In a Phase 2 trial, TZP significantly reduced HbA1c and body weight at 26 weeks (≥ 37% achieved 10% weight loss at 2 highest doses). Patients with T2D were randomly assigned (1:1:1:1:1:1) to receive either once-weekly sc TZP (1, 5, 10, or 15 mg), dulaglutide (1.5 mg), or placebo for 26 weeks. Because of the overlap of T2D and NAFLD populations, we measured several NASH related biomarkers to explore whether TZP may have potential efficacy in NASH. These included: ALT, AST, Keratin-18 M30 fragment (K-18, apoptosis marker; Peviva), Pro-C3 (fibrosis marker, a fragment of the NH2-terminal propeptide of type III procollagen; Nordic Bioscience), and adiponectin (adipokine that protects liver from inflammation and fibrosis; Pacific Biomarkers). Results (Table) were analyzed in a modified intent-to-treat population using a mixed model for repeated measures. Significant (p Disclosure M.L. Hartman: Employee; Self; Eli Lilly and Company. A. Sanyal: Consultant; Self; Ardelyx, Boehringer Ingelheim Pharmaceuticals, Inc., Exhalenz, Gilead Sciences, Inc., Hemoshear, Intercept Pharmaceuticals, Inc., Lilly, Mallinckrodt Pharmaceuticals, Nimbus Therapeutics, Nitto Denko, Novartis Pharmaceuticals Corporation, Pfizer Inc. Employee; Self; Sanyal Bio. Research Support; Self; Bristol-Myers Squibb Company, Conatus Pharmaceuticals Inc., Echosens, Galectin Therapeutics Inc., Immuron Ltd, Merck & Co., Inc., Salix Pharmaceuticals, Sequanna. Stock/Shareholder; Self; Akarna Therapeutics, GENFIT, Natural Shield, NewCo LLC, Tiziana. Other Relationship; Self; Elsevier, UpToDate. R. Loomba: Consultant; Self; Eli Lilly and Company, Novo Nordisk Inc. J.M. Wilson: Employee; Self; Eli Lilly and Company. R. Bray: Employee; Self; Eli Lilly and Company. A. Nikooienejad: Research Support; Self; Eli Lilly and Company. K.L. Duffin: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Pfizer Inc. D.A. Robins: Employee; Self; Eli Lilly and Company. A. Haupt: Employee; Self; Lilly Diabetes. Stock/Shareholder; Self; Lilly Diabetes. Funding Eli Lilly and Company

Initiating incretin hormone receptor agonist therapy at a low dose with gradual dose escalation may improve gastrointestinal (GI) tolerability. This randomized, double-blind, placebo-controlled study assessed the efficacy and tolerability of tirzepatide, using 3 different dose escalation algorithms in patients with type 2 diabetes compared with placebo after 12 weeks. The dose-escalations included 1 algorithm to achieve 12 mg top dose by the scheme of 4 mg and 8 mg, each for 4 weeks. The scheme for the first 15 mg top dose group (15 mg-1) was 2.5 mg for 2 weeks, followed by 5 mg for 2 weeks, and then 10 mg for 4 weeks. The scheme for the second 15 mg top dose group (15 mg-2) was 2.5 mg followed by 7.5 mg, each for 4 weeks. A total of 111 subjects were randomized. Mean age was 57.4 years, HbA1c was 8.4%, and BMI was 31.9 kg/m2. At Week 12, LS mean HbA1c% (SE) was 8.6 (0.21), 6.7 (0.19), 6.3 (0.20), 6.6 (0.19) in the placebo, 12 mg, 15 mg-1 and 15 mg-2 groups, respectively. Change from baseline (SE) in HbA1c was greater in tirzepatide groups compared with placebo (placebo, +0.2% [0.21]; 12 mg, -1.7% [0.19]; 15 mg-1, -2.0% [0.20]; 15 mg-2, -1.8% [0.19]). Weight loss was greater in tirzepatide groups compared with placebo (placebo, -0.5 kg [0.86]; 12 mg, -5.3 kg [0.78]; 15 mg-1, -5.5 kg [0.80] and 15 mg-2, -5.7 kg [0.79]). The total incidence of nausea, vomiting and/or diarrhea was 11.5% with placebo, and 48.3%, 57.1% and 46.4% with tirzepatide 12 mg, 15 mg-1, and 15 mg-2 groups, respectively. GI AEs were mild to moderate in intensity. Tirzepatide resulted in clinically meaningful improvements in glycemic control and weight loss. A lower starting dose and a longer dose-escalation period resulted in lower incidence of GI AEs than in a previously published Phase 2 study. Disclosure J.P. Frias: Advisory Panel; Self; Becton, Dickinson and Company, Eli Lilly and Company, Gilead Sciences, Inc., Sanofi. Consultant; Self; Echosens, Genentech, Inc., Johnson & Johnson Diabetes Institute, Novo Nordisk Inc., Zafgen, Inc. Research Support; Self; AbbVie Inc., Akcea Therapeutics, Allergan, Amgen Inc., AstraZeneca, Bayer US, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Cirius Therapeutics, Elcelyx Therapeutics, Inc., Eli Lilly and Company, Enanta Pharmaceuticals, Inc., GENFIT, Intarcia Therapeutics, Inc., Intercept Pharmaceuticals, Inc., Ionis Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., NGM Biopharmaceuticals, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Oramed Pharmaceuticals, Pfizer Inc., Sanofi, TaiwanJ Pharmaceuticals Co., Ltd., Theracos, Inc. Speaker's Bureau; Self; Merck & Co., Inc., Sanofi. M.A. Nauck: Advisory Panel; Self; AstraZeneca, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S. Research Support; Self; AstraZeneca, Eli Lilly and Company, GlaxoSmithKline plc., Merck Sharp & Dohme Corp., Novo Nordisk A/S. Speaker's Bureau; Self; AstraZeneca, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sun Pharma. J. Van: Research Support; Self; Eli Lilly and Company, Genentech, Inc., Melior, Merck & Co., Inc., Mylan, Oramed Pharmaceuticals, Sanofi. C. Benson: Employee; Self; Eli Lilly and Company. R. Bray: Employee; Self; Eli Lilly and Company. Z. Milicevic: Employee; Self; Eli Lilly and Company. A. Haupt: Employee; Self; Lilly Diabetes. Stock/Shareholder; Self; Lilly Diabetes. D.A. Robins: Employee; Self; Eli Lilly and Company. Funding Eli Lilly and Company