OBJECTIVEInsulin degludec (IDeg) is a basal insulin that forms soluble multihexamers after subcutaneous injection, resulting in an ultra-long action profile. We assessed the efficacy and safety of IDeg formulations administered once daily in combination with mealtime insulin aspart in people with type 1 diabetes.RESEARCH DESIGN AND METHODSIn this 16-week, randomized, open-label trial, participants (mean: 45.8 years old, A1C 8.4%, fasting plasma glucose [FPG] 9.9 mmol/L, BMI 26.9 kg/m2) received subcutaneous injections of IDeg(A) (600 μmol/L; n = 59), IDeg(B) (900 μmol/L; n = 60), or insulin glargine (IGlar; n = 59), all given once daily in the evening. Insulin aspart was administered at mealtimes.RESULTSAt 16 weeks, mean A1C was comparable for IDeg(A) (7.8 ± 0.8%), IDeg(B) (8.0 ± 1.0%), and IGlar (7.6 ± 0.8%), as was FPG (8.3 ± 4.0, 8.3 ± 2.8, and 8.9 ± 3.5 mmol/L, respectively). Estimated mean rates of confirmed hypoglycemia were 28% lower for IDeg(A) compared with IGlar (rate ratio [RR]: 0.72 [95% CI 0.52–1.00]) and 10% lower for IDeg(B) compared with IGlar (RR: 0.90 [0.65–1.24]); rates of nocturnal hypoglycemia were 58% lower for IDeg(A) (RR: 0.42 [0.25–0.69]) and 29% lower for IDeg(B) (RR: 0.71 [0.44–1.16]). Mean total daily insulin dose was similar to baseline. The frequency and pattern of adverse events was similar between insulin treatments.CONCLUSIONSIn this clinical exploratory phase 2 trial in people with type 1 diabetes, IDeg is safe and well tolerated and provides comparable glycemic control to IGlar at similar doses, with reduced rates of hypoglycemia.

To explore the efficacy, safety, and tolerability of once-weekly efpeglenatide, a long-acting glucagon-like peptide 1 receptor agonist (GLP-1 RA), in early type 2 diabetes (T2D) (drug naive or on metformin monotherapy). RESEARCH DESIGN AND METHODS EXCEED 203 was a 12-week, randomized, placebo-controlled, double-blind, parallelgroup, dose-ranging study of efpeglenatide once weekly referenced to open-label liraglutide 1.8 mg (exploratory analysis). Participants, ∼90% on metformin monotherapy, were randomized to one of five efpeglenatide doses (0.3, 1, 2, 3, or 4 mg q.w.; n = 181), placebo (n = 37), or liraglutide (£1.8 mg daily; n = 36). The primary efficacy end point was change in HbA 1c from baseline to week 13. RESULTS From a baseline HbA 1c of 7.7-8.0% (61.0-63.9 mmol/mol), all efpeglenatide doses ‡1 mg significantly reduced HbA 1c versus placebo (placebo-adjusted least squares [LS] mean changes 0.6-1.2%, P < 0.05 for all) to a final HbA 1c of 6.3-6.8% (45.4-50.6 mmol/mol); masked efpeglenatide 4 mg was noninferior to open-label liraglutide. Greater proportions treated with efpeglenatide ‡1 mg than placebo achieved HbA 1c <7% (61-72% vs. 24%, P < 0.05 for all), and greater reductions in body weight were observed with efpeglenatide 3 and 4 mg versus placebo (placeboadjusted LS mean differences 21.4 and 22.0 kg, respectively, P < 0.05 for both). Rates of nausea and vomiting were consistent with other GLP-1 RAs and rapidly subsided after the initial 2 weeks. No neutralizing antibodies were detected with efpeglenatide. CONCLUSIONS Efpeglenatide once weekly led to significant reductions in HbA 1c and weight, with a safety profile consistent with the GLP-1 RA class in patients with early T2D mostly on metformin monotherapy.

AimsThe efficacy and safety of insulin degludec (degludec), a new-generation ultra-long-acting basal insulin, was compared with insulin glargine (glargine) in people with Type 1 diabetes mellitus in a 16-week, open-label, randomized trial. Health status, an important aspect of effective diabetes management, was also assessed.MethodsDegludec (n = 59) or glargine (n = 59) were injected once daily, with insulin aspart at mealtimes. Health status assessment utilized the validated Short Form 36 Health Survey, version 2, which has two summary component scores for mental and physical well-being, each comprising four domains.ResultsAt study end, HbA1c reductions were comparable between groups, but confirmed nocturnal hypoglycaemia was significantly less frequent with degludec [relative rate 0.42 (95% CI 0.25–0.69)], and overall hypoglycaemia numerically less frequent [relative rate 0.72 (95% CI 0.52–1.00)]. After 16 weeks, a significant improvement in Short Form 36 Health Survey mental component score of +3.01 (95% CI 0.32–5.70) was obtained for degludec against glargine, attributable to significant differences in the social functioning [+8.04 (95% CI 1.89–14.18)] and mental health domains [+2.46 (95% CI 0.10–4.82)]. For mental component score, Cohen’s effect size was 0.42, indicating a small-to-medium clinically meaningful difference. The physical component score [+0.66 (95% CI –2.30 to 3.62)] and remaining domains were not significantly different between degludec and glargine.ConclusionsIn the context of comparable overall glycaemic control with glargine, degludec improved mental well-being as measured using the mental component score of the Short Form 36 Health Survey. The improvements in overall mental component score and the underlying social functioning and mental health domains with degludec compared with glargine may relate to the observed reduction in hypoglycaemic events.

No abstract

Once-weekly (QW), subcutaneous efpeglenatide (EFPEG) is a long-acting GLP-1 RA for T2D management. In EXCEED 203 (NCT02057172), EFPEG QW significantly reduced HbA1c vs. placebo (PBO) for early T2D (naïve/metformin monotherapy). This post hoc subanalysis explored the efficacy of EFPEG QW (pooled low [1 and 2 mg] or high dose [3 and 4 mg]) vs. PBO stratified by baseline characteristics: HbA1c (&lt;8%; 8‒9%; &gt;9%), BMI (&lt;30; ≥30 kg/m2), FPG, T2D duration, and age (&lt;median; ≥median). Change in HbA1c, FPG, and BMI from baseline to Week 13 was compared within and across baseline characteristic subgroups. Within subgroups, HbA1c and FPG reductions were significantly greater for patients with higher HbA1c at baseline with high-dose EFPEG (p≤0.0015) according to HbA1c and FPG subgroups; low-dose EFPEG followed the same trend in most cases. HbA1c and FPG reduction were similar for BMI, T2D duration, and age subgroups; BMI outcomes did not significantly differ within subgroups. There were numerically greater LS mean reductions in HbA1c and FPG from baseline vs. PBO, which were significant for high-dose EFPEG, for all subgroups (except HbA1c &gt;9% for FPG; Table); reductions were greater with high-dose vs. low-dose EFPEG. For BMI, there was a trend for reductions vs. PBO with high-dose EFPEG (Table). In conclusion, high-dose EFPEG demonstrated significant reductions in HbA1c vs. PBO for all baseline characteristic subgroups. Disclosure G.E. Dailey: Research Support; Self; Eli Lilly and Company, Novo Nordisk Inc., Sanofi US. Speaker's Bureau; Self; Sanofi US. J. Rosenstock: Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, Genentech, Inc., GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Melior Pharmaceuticals, Inc., Bukwang Pharm. Co., Ltd., Merck & Co., Inc., Oramed Pharmaceuticals, PegBio Co., Ltd., Pfizer Inc. Other Relationship; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. C. Morales: Other Relationship; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. U. Wendisch: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Eli Lilly and Company, Kowa Pharmaceutical Europe Co. Ltd., Lexicon Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S. Stock/Shareholder; Self; Novartis AG, Novo Nordisk A/S. M.E. Trautmann: Consultant; Self; CeQur Corporation, Hanmi Pharm. Co., Ltd., Intarcia Therapeutics, Inc., Oramed Pharmaceuticals, ProSciento, Servier. Stock/Shareholder; Self; Lilly Diabetes. M. Hompesch: Stock/Shareholder; Self; ProSciento. I. Choi: Employee; Self; Hanmi Pharm. Co., Ltd. J. Kang: Employee; Self; Hanmi Pharm. Co., Ltd. C.H. Sorli: Employee; Self; Sanofi. I. Ogbaa: Stock/Shareholder; Self; Lexicon Pharmaceuticals, Inc. Other Relationship; Self; Sanofi. J.A. Stewart: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. K. Yoon: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc. Speaker's Bureau; Self; Takeda Pharmaceutical Company Limited. Funding Hanmi Pharmaceutical, Co., Ltd.; Sanofi

Efpeglenatide (EFPEG) is a long-acting GLP-1 RA, administered by once-weekly (QW) subcutaneous injection, currently being developed to improve glycemic control in patients with T2D. EXCEED 203 (NCT02057172), a 12-week study of EFPEG (0.3, 1, 2, 3, or 4 mg QW) compared with placebo (PBO) and referenced to open-label liraglutide 1.8 mg in uncontrolled T2D (naïve/metformin monotherapy), found significantly improved HbA1c for all doses of EFPEG ≥1 mg, and reductions in body weight for EFPEG 3 and 4 mg. This exploratory subanalysis investigated any potential relationship between glycemic control and weight loss effects observed in EXCEED 203. At all EFPEG doses ≥1 mg and in two combined populations (low-dose group: EFPEG 1 and 2 mg; high-dose group: EFPEG 3 and 4 mg) vs. PBO, greater proportions of patients significantly achieved the composite endpoint of HbA1c &lt;7% and weight loss &gt;3 kg (p&lt;0.05 for all; Table). Linear regression analysis revealed no correlation between change in HbA1c and change in body weight throughout the study for all EFPEG doses ≥1 mg. EFPEG was well tolerated with adverse events mirroring those known for GLP-1 RAs. In conclusion, EFPEG was associated with greater proportions of patients achieving the composite endpoint of HbA1c &lt;7% and weight loss &gt;3 kg vs. PBO without evidence that the glucose-lowering effects of EFPEG were dependent on weight loss. Disclosure J. Rosenstock: Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, Genentech, Inc., GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Melior Pharmaceuticals, Inc., Bukwang Pharm. Co., Ltd., Merck & Co., Inc., Oramed Pharmaceuticals, PegBio Co., Ltd., Pfizer Inc. Other Relationship; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. C. Morales: Other Relationship; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. U. Wendisch: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Eli Lilly and Company, Kowa Pharmaceutical Europe Co. Ltd., Lexicon Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S. Stock/Shareholder; Self; Novartis AG, Novo Nordisk A/S. G.E. Dailey: Research Support; Self; Eli Lilly and Company, Novo Nordisk Inc., Sanofi US. Speaker's Bureau; Self; Sanofi US. M.E. Trautmann: Consultant; Self; CeQur Corporation, Hanmi Pharm. Co., Ltd., Intarcia Therapeutics, Inc., Oramed Pharmaceuticals, ProSciento, Servier. Stock/Shareholder; Self; Lilly Diabetes. M. Hompesch: Stock/Shareholder; Self; ProSciento. I. Choi: Employee; Self; Hanmi Pharm. Co., Ltd. J. Kang: Employee; Self; Hanmi Pharm. Co., Ltd. J.A. Stewart: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. I. Ogbaa: Stock/Shareholder; Self; Lexicon Pharmaceuticals, Inc. Other Relationship; Self; Sanofi. C.H. Sorli: Employee; Self; Sanofi. K. Yoon: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc. Speaker’s Bureau; Self; Takeda Pharmaceutical Company Limited. Funding Hanmi Pharmaceutical, Co., Ltd.; Sanofi

No abstract