The journey to understanding incretin systems: Theory, practice and more theory

Yabe, Daisuke; Kuwata, Hitoshi; Seino, Yutaka

doi:10.1111/jdi.13123

Cited by 5 publications

(3 citation statements)

References 17 publications

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“…It is known that a weight loss of 5% or more is associated with improved glycaemic control in patients with T2D, and weight loss is therefore a cornerstone of T2D treatment 7,13,14 . The pathophysiology of T2D in East Asians involves reduced insulin secretory capacity and less insulin resistance compared with Caucasians 15–17 …”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of once‐weekly semaglutide versus once‐daily sitagliptin as add‐on to metformin in patients with type 2 diabetes in SUSTAIN China: A 30‐week, double‐blind, phase 3a, randomized trial

Dong

et al. 2021

Diabetes Obesity Metabolism

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Aim To evaluate the efficacy and safety of once‐weekly subcutaneous semaglutide, a glucagon‐like peptide‐1 (GLP‐1) analogue, versus once‐daily sitagliptin as add‐on to metformin in patients with type 2 diabetes (T2D) in a multiregional clinical trial. Materials and Methods In the 30‐week, randomized, double‐blind, double‐dummy, active comparator SUSTAIN China trial, 868 adults with T2D inadequately controlled on metformin (HbA1c 7.0%‐10.5%) were randomized to receive once‐weekly semaglutide 0.5 mg (n = 288), semaglutide 1.0 mg (n = 290) or once‐daily sitagliptin 100 mg (n = 290). The primary and confirmatory secondary endpoints were change from baseline to week 30 in HbA1c and body weight, respectively. Results The trial enrolled ~70% (605/868) of the patients in China, and the remaining patients from four other countries, including the Republic of Korea. Both doses of semaglutide were superior to sitagliptin in reducing HbA1c and body weight after 30 weeks of treatment. The odds of achieving target HbA1c of less than 7.0% (53 mmol/mol), weight loss of 5% or higher, or 10% or higher, and the composite endpoint of HbA1c less than 7.0% (53 mmol/mol) without severe or blood glucose‐confirmed symptomatic hypoglycaemia no weight gain, were all significantly higher with both semaglutide doses compared with sitagliptin. The safety profile for semaglutide was consistent with the known class effects of GLP‐1 receptor agonists (RAs). Consistent efficacy and safety findings were seen in the Chinese subpopulation. Conclusions Once‐weekly semaglutide was superior to sitagliptin in improving glycaemic control and reducing body weight in patients with T2D inadequately controlled on metformin. The safety and tolerability profiles were consistent with those of semaglutide and other GLP‐1 RAs. Semaglutide is an effective once‐weekly treatment option for the Chinese population.

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Section: Introductionmentioning

confidence: 99%

Efficacy and safety of once‐weekly semaglutide versus once‐daily sitagliptin as add‐on to metformin in patients with type 2 diabetes in SUSTAIN China: A 30‐week, double‐blind, phase 3a, randomized trial

Dong

et al. 2021

Diabetes Obesity Metabolism

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“…Gut microbiota convert undigested carbohydrates into short-chain fatty acids (SCFA), 5 metabolites which stimulate intestinal L cells to secrete incretin hormones (GLP-1, GLP-2 and PYY) that trigger pancreatic beta-cells to release insulin. 6 Dysbiosis decreases intestinal wall integrity and induces systemic low-grade inflammation. This metabolic endotoxemia state is precipitated by the dependent attachment of lipopolysaccharide (LPS) to the CD14 / toll-like receptor (TLR) 4 complex on the surface of intestinal cells leading to inflammation and subsequent insulin resistance.…”

Section: Methodsmentioning

confidence: 99%

Review of Literature on Akkermansia muciniphila and its Possible Role in the Etiopathogenesis and Therapy of Type 2 Diabetes Mellitus

Sanjiwani

Aryadi

Semadi

2022

JAFES

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Akkermansia muciniphila is a promising gut microbiota for the treatment of type 2 diabetes mellitus (T2DM). A. muciniphila stimulates intestinal wall integrity, is an anti-inflammatory agent, and reduces endoplasmic reticulum stress, lipogenesis and gluconeogenesis. These properties make A. muciniphila a potential treatment option for T2DM by reducing insulin resistance and increasing insulin sensitivity and glucose tolerance in different tissues. This article explores the possible role of A. muciniphila in T2DM management, along with the various methods known to modulate A. muciniphila .

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“…The glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1RA) has been gaining attention as an anti-diabetes drug with cardiovascular and renal benefits [1][2][3][4] . Preclinical and clinical studies have demonstrated that GLP-1 ameliorates secretions of insulin and glucagon and delays gastric emptying, thereby improving postprandial glucose excursion [5][6][7] .…”

Section: Introductionmentioning

confidence: 99%

Effects of glucagon‐like peptide‐1 receptor agonists on secretions of insulin and glucagon and gastric emptying in Japanese individuals with type 2 diabetes: A prospective, observational study

Kuwata

Yabe

Murotani

et al. 2021

J of Diabetes Invest

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Aims/Introduction: Differences in the glucose-lowering mechanisms of glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been noted. Clarifying these differences could facilitate the choice of optimal drugs for individuals with type 2 diabetes and requires investigation in a clinical setting. Materials and Methods: A single-arm, prospective, observational study was conducted to evaluate the effects of various GLP-1RAs on postprandial glucose excursion, secretions of insulin and glucagon as well as on the gastric emptying rate. Participants were subjected to meal tolerance tests before and 2 weeks and 12 weeks after GLP-1RA initiation. Effects on postprandial secretions of glucose-dependent insulinotropic polypeptide (GIP) and apolipoprotein B48 were also investigated. Results: Eighteen subjects with type 2 diabetes received one of three GLP-1RAs, i.e., lixisenatide, n = 7; liraglutide, n = 6; or dulaglutide, n = 5. While 12-week administration of all of the GLP-1RAs significantly reduced HbA1c, only lixisenatide and liraglutide, but not dulaglutide, significantly reduced body weight. Postprandial glucose elevation was improved by all of the GLP-1RAs. Postprandial insulin levels were suppressed by lixisenatide, while insulin levels were enhanced by liraglutide. Postprandial glucagon levels were suppressed by lixisenatide. The gastric emptying rate was significantly delayed by lixisenatide, while liraglutide and dulaglutide had limited effects on gastric emptying. GIP secretion was suppressed by lixisenatide and liraglutide. Apolipoprotein B48 secretion was suppressed by all of the GLP-1RAs. Conclusions: All of the GLP-1RAs were found to improve HbA1c in a 12-week prospective observational study in Japanese individuals with type 2 diabetes. However, differences in the mechanisms of the glucose-lowering effects and body weight reduction were observed.

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The journey to understanding incretin systems: Theory, practice and more theory

Cited by 5 publications

References 17 publications

Efficacy and safety of once‐weekly semaglutide versus once‐daily sitagliptin as add‐on to metformin in patients with type 2 diabetes in SUSTAIN China: A 30‐week, double‐blind, phase 3a, randomized trial

Efficacy and safety of once‐weekly semaglutide versus once‐daily sitagliptin as add‐on to metformin in patients with type 2 diabetes in SUSTAIN China: A 30‐week, double‐blind, phase 3a, randomized trial

Review of Literature on Akkermansia muciniphila and its Possible Role in the Etiopathogenesis and Therapy of Type 2 Diabetes Mellitus

Effects of glucagon‐like peptide‐1 receptor agonists on secretions of insulin and glucagon and gastric emptying in Japanese individuals with type 2 diabetes: A prospective, observational study

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