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How to fight obesity with antidiabetic drugs: targeting gut or kidney?

作者信息

Baretić M, Troskot R

机构信息

Division of Endocrinology Department of Internal Medicine, University Hospital Centre Zagreb, Croatia -

出版信息

Minerva Endocrinol. 2015 Mar;40(1):71-83. Epub 2014 Nov 4.


DOI:
PMID:25366984
Abstract

The increased prevalence of type 2 diabetes follows the increased prevalence of obesity. Both diseases share common pathophysiological pathways; obesity is in most cases the first step, whereas diabetes is the second one. Weight gain occurs during the treatment of diabetes with drugs causing endogenous or exogenous hyperinsulinemia. Insulin and sulfonylurea are making patients more obese and more insulin resistant. Glucagon-like peptide-1 receptor agonists (GLP-1 agonists) and sodium/glucose cotransporter 2 inhibitors (SGLT2 inhibitors) are antidiabetic drugs with weight loss property. GLP-1 agonists mimic an incretin action. They release insulin after a meal during hyperglycemia and suppress glucagon. The weight loss effect is a consequence of central action increased satiety. Some of GLP-1 agonists weight loss is a result of decelerated gastric emptying rate. SGLT2 inhibitors block sodium glucose cotransporter in proximal tubule brush border and produce glucose excretion with urinary loss. Urinary glucose leak results in calories and weight loss. Even a modest weight loss has positive outcome on metabolic features of diabetic patient; such drugs have important role in treatment of type 2 diabetic patients. However, there are some still unresolved questions. The weight loss they produce is modest. Those drugs are expensive and not available to many diabetic patients, they are significantly more expensive compared to "traditional" hypoglycemic drugs. The hypoglycemic endpoint of GLP-1 agonists and SGLT2 inhibitors often requires adding another antidiabetic drug. The most radical and most effective therapy of type 2 diabetes and obesity is bariatric surgery having significant number of diabetes remission.

摘要

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引用本文的文献

[1]
Impact of Cotadutide drug on patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

BMC Endocr Disord. 2022-4-29

[2]
GLUCAGON-LIKE PEPTIDE-1 AFFECTS TASTE PERCEPTION DIFFERENTLY IN WOMEN: A RANDOMIZED, PLACEBO-CONTROLLED CROSSOVER STUDY.

Acta Clin Croat. 2019-6

[3]
Therapy to Obese Type 2 Diabetes Mellitus: How Far Will We Go Down the Wrong Road?

Chin J Integr Med. 2020-1

[4]
MEDI0382, a GLP-1/glucagon receptor dual agonist, meets safety and tolerability endpoints in a single-dose, healthy-subject, randomized, Phase 1 study.

Br J Clin Pharmacol. 2018-8-7

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