Insulin Secretion

Meier, Juris J.

doi:10.1016/b978-0-323-18907-1.00032-9

Cited by 4 publications

(2 citation statements)

References 183 publications

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“…Type 2 diabetes (T2D) is one of the most common chronic diseases, characterized by pancreatic β‐cell dysfunction and insulin resistance leading to chronic hyperglycaemia 1,2 . Recent estimates indicate that there were 422 million adults in the world with T2D in 2014 compared with 108 million adults in 1980 3 .…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of imeglimin in Japanese patients with type 2 diabetes: A 24‐week, randomized, double‐blind, placebo‐controlled, dose‐ranging phase 2b trial

Dubourg

Ueki

Grouin

et al. 2021

Diabetes Obesity Metabolism

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Aim To assess the efficacy and safety of imeglimin monotherapy compared with placebo for 24 weeks in Japanese patients with type 2 diabetes (T2D). Materials and Methods In this 24‐week, randomized, double‐blind, placebo‐controlled, parallel‐group, dose‐ranging, phase 2b clinical trial, Japanese adults (age ≥ 20 years) with T2D either treatment‐naïve or previously treated with one oral antidiabetes agent were eligible for participation. Patients were randomly assigned (1:1:1:1) to receive orally imeglimin 500, 1000 or 1500 mg, or placebo twice‐daily over a 24‐week period. The primary endpoint was the placebo‐adjusted change at week 24 in HbA1c. Safety outcomes were assessed in all patients who received at least one dose of study drug. Results A total of 299 patients were randomized to receive double‐blind treatment with orally twice‐daily placebo (n = 75), imeglimin 500 mg (n = 75), 1000 mg (n = 74) or 1500 mg (n = 75). At week 24, imeglimin significantly decreased HbA1c (difference vs. placebo: imeglimin 500 mg −0.52% [95% CI: −0.77%, −0.27%], imeglimin 1000 mg −0.94% [95% CI: −1.19%, −0.68%], imeglimin 1500 mg −1.00% [95% CI: −1.26%, −0.75%]; P < .0001 for all). Treatment‐emergent adverse events were reported for 68.0%, 62.2%, 73.3% and 68.0% of patients receiving imeglimin 500, 1000 or 1500 mg and placebo, respectively. A small increase in gastrointestinal adverse effects (e.g. diarrhoea) occurred with the 1500 mg dose level. Hypoglycaemia was balanced among groups. Conclusions Imeglimin as monotherapy in Japanese patients with T2D was well tolerated and significantly improved glycaemic control with no significant increase in hypoglycaemic events versus placebo. Given the marginal increase in efficacy with the 1500 versus 1000 mg dose (along with the potential for gastrointestinal tolerability issues), a dose of 1000 mg twice‐daily was selected for subsequent phase 3 studies.

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Section: Introductionmentioning

confidence: 99%

Efficacy and safety of imeglimin in Japanese patients with type 2 diabetes: A 24‐week, randomized, double‐blind, placebo‐controlled, dose‐ranging phase 2b trial

Dubourg

Ueki

Grouin

et al. 2021

Diabetes Obesity Metabolism

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“…The regulation of insulin secretion and circulating levels is highly complex, reflecting β cell mass and secretion. Among the regulators of insulin secretion, glucose is the most important, but other nutrients (free fatty acids, amino acids), hormones (GLP-1, GIP), and sympathetic and cholinergic autonomic influences play important roles in acute regulation of hormone levels ( 72 ). The rapid rise of insulin with feeding promotes uptake and storage of ingested energy in fat and muscle, and it suppresses hepatic glucose production, together keeping postprandial blood glucose levels from rising excessively.…”

Section: Physiology and Pathophysiology Of Insulin And Leptinmentioning

confidence: 99%

Starvation in the Midst of Plenty: Reflections on the History and Biology of Insulin and Leptin

Flier

2018

Endocrine Reviews

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Insulin and leptin are critical metabolic hormones that play essential but distinct roles in regulating the physiologic switch between the fed and starved states. The discoveries of insulin and leptin, in 1922 and 1994, respectively, arose out of radically different scientific environments. Despite the dearth of scientific tools available in 1922, insulin’s discovery rapidly launched a life-saving therapy for what we now know to be type I diabetes, and continually enhanced insulin therapeutics are now effectively applied to both major forms of this increasingly prevalent disease. In contrast, although the discovery of leptin provided deep insights into the regulation of central nervous system energy balance circuits, as well as an effective therapy for an extremely rare form of obesity, its therapeutic impact beyond that has been surprisingly limited. Despite an enormous accumulated body of information, many important questions remain unanswered about the mechanisms of action and role in disease of both hormones. Additionally, although many decades apart, both discoveries reveal the complexities inherent to scientific collaboration and the assignment of credit, even when the efforts are spectacularly successful.

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Pancreatic Gland Therapies

2023

Endocrinology

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Insulin Secretion

Cited by 4 publications

References 183 publications

Efficacy and safety of imeglimin in Japanese patients with type 2 diabetes: A 24‐week, randomized, double‐blind, placebo‐controlled, dose‐ranging phase 2b trial

Efficacy and safety of imeglimin in Japanese patients with type 2 diabetes: A 24‐week, randomized, double‐blind, placebo‐controlled, dose‐ranging phase 2b trial

Starvation in the Midst of Plenty: Reflections on the History and Biology of Insulin and Leptin

Pancreatic Gland Therapies

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