Drug Development Strategy for Type 2 Diabetes: Targeting Positive Energy Balances.

Abstract:

:Newer classes of medications have been proven useful in glycemic control in type 2 diabetes (T2D), but many do not appear capable to slow down the progressive loss of ß-cell function, or to improve population-level glycemic control. Positive energy balance, e.g. surplus energy intake over expenditure, is at the core for developing metabolic syndrome and T2D. Currently available glycemic control drugs come to the market based on their 1-2 years risk-benefit profiles, but most of them do not correct positive energy balance and lose efficacy in the long-term. This denouement is destined by a positive energy balance of T2D. There is continuous endeavor/investment in new drugs for T2D. In this review, we compared the effects of commonly used oral hypoglycemic agents on energy balance and discussed several novel therapeutic targets/approaches for T2D that could potentially correct positive energy balance: changing the composition of intestinal host-microbiota to alleviate excess caloric consumption, controlling chylomicron uptake into intestinal lacteals to reduce excessive caloric intake, and activating pyruvate kinase M2 (PKM2) to ameliorate glucose metabolism and increase energy expenditure. We further reviewed how nicotine affects body weight and ameliorates positive energy balance, and ways to encourage people to adopt a more healthy lifestyle by exercising more and/or decreasing caloric intake. These potential targets/approaches may hopefully correct positive energy balance, delay disease progression, reverse some pathophysiological changes, and eventually prevent and/or cure the disease. Drug development strategies applying new insights into T2D process and therapeutic index to correct positive energy balance need to be seriously considered.

journal_name

Curr Drug Targets

journal_title

Current drug targets

authors

Liu Z,Yang B

doi

10.2174/1389450120666181217111500

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

879-890

issue

8

eissn

1389-4501

issn

1873-5592

pii

CDT-EPUB-95256

journal_volume

20

pub_type

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