Relationship between diet/exercise and pharmacotherapy to enhance the GLP‐1 levels in type 2 diabetes

Abstract

The rapid rise in the prevalence of type 2 diabetes mellitus (T2DM) poses a huge healthcare burden across the world. Although there are several antihyperglycaemic agents (AHAs) available including addition of new drug classes to the treatment algorithm, more than 50% of patients with T2DM do not achieve glycaemic targets, suggesting an urgent need for treatment strategies focusing on prevention and progression of T2DM and its long‐term complications. Lifestyle changes including implementation of healthy diet and physical activity are cornerstones for the management of T2DM. The positive effects of diet and exercise on incretin hormones such as glucagon‐like peptide‐1 (GLP‐1) have been reported. We hypothesize an IDEP concept (Interaction between Diet/Exercise and Pharmacotherapy) aimed at modifying the diet and lifestyle, along with pharmacotherapy to enhance the GLP‐1 levels, would result in good glycaemic control in patients with T2DM. Consuming protein‐rich food, avoiding saturated fatty acids and making small changes in eating habits such as eating slowly with longer mastication time can have a positive impact on the GLP‐1 secretion and insulin levels. Further the type of physical activity (aerobic/resistance training), intensity of exercise, duration, time and frequency of exercise have shown to improve GLP‐1 levels. Apart from AHAs, a few antihypertensive drugs and lipid‐lowering drugs have also shown to increase endogenous GLP‐1 levels, however, due to quick degradation of GLP‐1 by dipeptidyl peptidase‐4 (DPP‐4) enzyme, treatment with DPP‐4 inhibitors would protect GLP‐1 from degradation and prolong its activity. Thus, IDEP concept can be a promising treatment strategy, which positively influences the GLP‐1 levels and provide additive benefits in terms of improving metabolic parameters in patients with T2DM and slowing the progression of T2DM and its associated complications.

Teneligliptin Promotes Bile Acid Synthesis and Attenuates Lipid Accumulation in Obese Mice by Targeting the KLF15-Fgf15 Pathway

“…14 Various studies have demonstrated the benefit of increased GLP-1 expression induced by BAs in type II diabetes and other diseases. 15 Recent research suggests that teneligliptin could prevent obesity by enhancing the function of brown adipose tissue, which may be mediated by BAs, as BAs are known to promote brown adipose activity. 16,17 In the present study, we postulated that teneligliptin could improve BA synthesis.…”

“…DPP-4 rapidly degrades circulating glucagon-like peptide-1 (GLP-1), a gut-derived hormone involved in insulin secretion, metabolism, and satiety. , BAs have been shown to induce the expression of GLP-1 through the activation of G protein-coupled bile acid receptor TGR5, thereby improving glucose metabolism . Various studies have demonstrated the benefit of increased GLP-1 expression induced by BAs in type II diabetes and other diseases . Recent research suggests that teneligliptin could prevent obesity by enhancing the function of brown adipose tissue, which may be mediated by BAs, as BAs are known to promote brown adipose activity. , In the present study, we postulated that teneligliptin could improve BA synthesis.…”

The glucose tolerance test in mice: sex, drugs and protocol.

“…However, administration of glucose by the mice voluntarily ingesting glucose gels led to lower glucose peaks post administration compared to oral gavage. Although we cannot rule out the possibility of enhanced incretin effects with glucose gels due to chewing, the differences observed are also likely to be associated with the reduced stress of voluntary gel consumption (Fujiwara et al, 2019).…”

AGP und Ernährung – Mit CGM postprandiale Glukoseverläufe analysieren

“…1) [31]. Neben Insulinen sollte auch der Einfluss anderer glukosesenkender Therapeutika auf postprandiale Glukoseanstiege, die u. a. infolge einer Veränderung der Sekretion von Darmhormonen und/ oder einer Verzögerung der Magenentleerung entstehen, berücksichtigt werden [33].…”