Background: Recent trials have shown improved CV outcomes in patients with type 2 diabetes (T2D) treated with specific glucose-lowering medications, but the potential real-world impact of such ...strategies is largely unknown.
Abstract
Disclosure: J.P. Frias: Advisory Board Member; Self; Corcept Therapeutics. Consulting Fee; Self; Corcept Therapeutics. Other; Self; Corcept Therapeutics. R.J. Auchus: Consulting Fee; Self; ...Corcept Therapeutics. Grant Recipient; Self; Corcept Therapeutics. Speaker; Self; Corcept Therapeutics. Other; Self; Corcept Therapeutics. I. Bancos: None. L. Blonde: Advisory Board Member; Self; Corcept Therapeutics. Other; Self; Corcept Therapeutics. R.S. Busch: Consulting Fee; Self; Corcept Therapeutics. Speaker; Self; Bayer, Inc., Novo Nordisk, Amgen Inc, Eli Lilly & Company, AstraZeneca. J.B. Buse: Advisory Board Member; Self; AstraZeneca, Bayer, Inc., Boehringer Ingelheim, Eli Lilly & Company, Jansen Pharmaceuticals, Mannkind Corporation, Sanofi, Alkahest, Altimmune, Anji, Biomea Fusion Inc, CeQur, Cirius Therapeutics Inc, GentiBio, Glycadia, Glyscend, Mellitus Health, Moderna, Pendulum Therapeutics, Praetego, Stability Health, Valo, Zealand Pharma. Consulting Fee; Self; AstraZeneca, Bayer, Inc., Boehringer Ingelheim, Eli Lilly & Company, Janssen, Mannkind Corporation, Sanofi, Alkahest, Altimmune, Anji, Biomea Fusion Inc, CeQur, Cirius Therapeutics Inc, Dasman Diabetes Center (Kuwait), Fortress Biotech, GentiBio, Glycadia, Glyscend, Mediflix, Medscape, Mellitus Health, Moderna, Pendulum Therapeutics, Praetego, ReachMD, Stability Health, Valo, Zealand Pharma. Grant Recipient; Self; Novo Nordisk, Sanofi, VTV Therapeutics, Nanotype, NIH, NovaTarg, Tolerion, Dexcom. Stock Owner; Self; Glyscend, Mellitus Health, Pendulum Therapeutics, PhaseBio, Praetego, Stability Health. Other; Self; AstraZeneca, Boehringer Ingelheim, Eli Lilly & Company, Novo Nordisk, Dasman Diabetes Institute, Zealand, Association for Clinical and Translational Science. R.A. DeFronzo: None. J.W. Findling: Advisory Board Member; Self; Corcept Therapeutics. Consulting Fee; Self; Corcept Therapeutics. V. Fonseca: Advisory Board Member; Self; Corcept Therapeutics. Consulting Fee; Self; Corcept Therapeutics. O. Hamidi: Advisory Board Member; Self; Corcept Therapeutics, Lantheus, Recordati Rare Diseases, Neurocrine Biosciences, Amryt, Novo Nordisk, Strongbridge. Consulting Fee; Self; Corcept Therapeutics. Y. Handelsman: Consulting Fee; Self; Amgen Inc, Applied Therapeutic, AstraZeneca, Bayer, Inc., Boehringer Ingelheim, Corcept Therapeutics, Esperion, Mannkind Corporation, Merck, Pfizer, Inc., Novartis Pharmaceuticals, Novo Nordisk, Sanofi, Vertis. Grant Recipient; Self; Amgen Inc, Applied Therapeutic, Ionis Pharmaceuticals Inc., Regor. Speaker; Self; AstraZeneca, Bayer, Inc., Esperion, Novo Nordisk, Vertis, Amarin. R.E. Pratley: Consulting Fee; Self; Bayer, Inc., Corcept Therapeutics, Gasherbrum Bio, Inc, Hanmi, Hengrui (USA) Ltd, Merck, Novo Nordisk, Pfizer, Inc., Rivus Pharmaceuticals Inc, Sun Pharmaceutical Industries, Sanofi, Scohia Pharma Inc, Dexcom. Grant Recipient; Self; Hanmi, Metavention, Novo Nordisk, Poxel SA. Speaker; Self; Novo Nordisk. J. Rosenstock: Advisory Board Member; Self; Applied Therapeutics, Boehringer Ingelheim, Eli Lilly & Company, Hanmi, Novo Nordisk, Oramed, Sanofi, Structure Therapeutics, Zealand. Consulting Fee; Self; Applied Therapeutics, Boehringer Ingelheim, Eli Lilly & Company, Hanmi, Novo Nordisk, Oramed, Sanofi, Structure Therapeutics, Zealand. Grant Recipient; Self; Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly & Company, Hanmi, Merck, Oramed, Novartis Pharmaceuticals, Novo Nordisk, Pfizer, Inc., Sanofi. I. Tudor: Employee; Self; Corcept Therapeutics. Stock Owner; Self; Corcept Therapeutics. A.G. Moraitis: Employee; Self; Corcept Therapeutics. D. Einhorn: Employee; Self; Corcept Therapeutics.
Studies suggest that the prevalence of hypercortisolism in persons with difficult-to-control type 2 diabetes (T2D) is higher than is currently appreciated. A recently published meta-analysis suggests that the prevalence of hypercortisolism is higher in persons with T2D who require a greater number of antihyperglycemic agents and/or who have more comorbidities. To better understand the prevalence and whether treatment of hypercortisolism may result in better control of diabetes and other hypercortisolism-associated comorbidities, we describe a 2-part phase 4 study in adults with difficult-to-control T2D (HbA1c 7.5-11.5%) despite receiving multiple antihyperglycemic agents. The study will be conducted at approximately 30 sites in the United States. In Part 1, approximately 1000 persons with difficult-to-control T2D will be screened with a 1-mg dexamethasone suppression test. Those responding with serum cortisol >1.8 µg/dL (50 nmol/L) and dexamethasone levels ≥140 ng/dL (3.6 nmol/L) will have adrenocorticotropic hormone (ACTH), dehydroepiandrosterone sulfate, and cortisol measured in fasting blood samples obtained between 7-9 AM and a non-contrast adrenal computed tomography scan. Patients who may have ACTH-dependent hypercortisolism will be discontinued from the study and referred for further evaluation. The primary study endpoint is determining the prevalence of ACTH-independent hypercortisolism and will be evaluated in Part 1. Patients identified to have ACTH-independent hypercortisolism will advance to Part 2, a prospective, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of treatment with the glucocorticoid receptor antagonist mifepristone. Patients will be randomized 2:1 to mifepristone or placebo, stratified by the presence or absence of adrenal adenomas on CT, and receive treatment for 24 weeks. The mifepristone dose will be 300 mg once daily for 4 weeks, then increased to 600 mg daily for 20 weeks based on clinical assessment of tolerability and degree of improvement. There will be an option to increase to mifepristone 900 mg. Placebo will be titrated accordingly from 1 up to 3 tablets. Part 2 will assess the secondary endpoint of change in HbA1c from baseline to 24 weeks, as well as changes in hypercortisolism-related comorbidities (e.g., blood pressure, weight, waist circumference, quality of life). This will be the first prospective study to assess the prevalence of ACTH-independent hypercortisolism in persons with difficult-to-control T2D and the first prospective, randomized, placebo-controlled trial to assess the potential benefits and safety of treatment with mifepristone in this patient population.
Presentation: Friday, June 16, 2023
Meta-analysis to compare hypoglycemia rates of basal insulin degludec (IDeg) with insulin glargine (IGlar) in patients with diabetes achieving good glycemic control (hemoglobin A1c HbA1c <7% at end ...of trial).
In a preplanned meta-analysis, patient data from 7 randomized, treat-to-target, 26- or 52-week trials in patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) who administered IDeg (n = 2,899) or IGlar (n = 1,431) once daily were analyzed. Using a negative binomial regression model, this meta-analysis compared hypoglycemia rates in patients achieving HbA1c <7% at end of trial with IDeg (n = 1,347) and IGlar (n = 697).
In all trials, IDeg was noninferior to IGlar in HbA1c reduction from baseline. At end of trial, 2,044 patients (T2DM, n = 1,661; T1DM, n = 383) achieved HbA1c <7%. The overall confirmed hypoglycemia rate, defined as plasma glucose <56 mg/dL or severe hypoglycemia if requiring assistance, was significantly lower with IDeg versus IGlar (estimated rate ratio ERR IDeg:IGlar, 0.86; 95% confidence interval CI, 0.76 to 0.98). The nocturnal confirmed hypoglycemia rate, defined as occurring between midnight and 6:00 am, was significantly lower with IDeg (ERR, 0.63; 95% CI, 0.52 to 0.77). In the maintenance period (16 weeks onward when average insulin dose and glycemic levels stabilized), the overall confirmed hypoglycemia rate was significantly lower (ERR, 0.79; 95% CI, 0.68 to 0.92) and the nocturnal confirmed hypoglycemia rate was significantly lower (ERR, 0.57; 95% CI, 0.45 to 0.72) with IDeg versus IGlar.
Patients with T1DM and T2DM achieved HbA1c <7% with significantly lower rates of overall and nocturnal confirmed hypoglycemia with IDeg versus IGlar. The lower hypoglycemia rate with IDeg was more pronounced in the maintenance period.
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