Acute Effect of Metformin on Postprandial Hypertriglyceridemia through Delayed Gastric Emptying

Abstract

Postprandial hypertriglyceridemia is a potential target for cardiovascular disease prevention in patients with diabetic dyslipidemia. Metformin has been reported to reduce plasma triglyceride concentrations in the postprandial states. However, little is known about the mechanisms underlying the triglyceride-lowering effect of metformin. Here, we examined the effects of metformin on lipid metabolism after olive oil-loading in 129S mice fed a high fat diet for three weeks. Metformin administration (250 mg/kg) for one week decreased postprandial plasma triglycerides. Pre-administration (250 mg/kg) of metformin resulted in a stronger triglyceride-lowering effect (approximately 45% lower area under the curve) than post-administration. A single administration (250 mg/kg) of metformin lowered plasma postprandial triglycerides comparably to administration for one week, suggesting an acute effect of metformin on postprandial hypertriglyceridemia. To explore whole body lipid metabolism after fat-loading, stomach size, fat absorption in the intestine, and fat oxidation (13C/12C ratio in expired CO2 after administration of glyceryl-1-13C tripalmitate) were measured with and without metformin (250 mg/kg) pre-treatment. In metformin-treated mice, larger stomach size, lower fat oxidation, and no change in lipid absorption were observed. In conclusion, metformin administration before fat loading reduced postprandial hypertriglyceridemia, most likely by delaying gastric emptying.

Efficacy of metformin on postprandial plasma triglyceride concentration by administration timing in patients with type 2 diabetes mellitus: A randomized cross‐over pilot study

“…In particular, participants with a larger reduction in AUC 0–4 h for glucose showed larger effects on AUC 0–4 h for TG. These findings are in agreement with those of our previous pre‐clinical study in which pre‐Met administration lowered plasma TG and glucose levels in mice. Furthermore, the present findings are consistent with a previous clinical study that showed lower glucose concentrations with pre‐Met administration before oral glucose tolerance testing.…”

“…This effect, similar to its glucose‐lowering effect, was reported to be dose‐dependent. Recently, we found that the administration of high‐dose metformin before fat loading significantly reduced postprandial plasma TG levels compared with administration after fat loading in an animal model. We therefore concluded that the major mechanism underlying the TG‐lowering effect of metformin is a reduction in intestinal absorption through delayed gastric emptying, and not an increase in fat oxidation in the peripheral tissues.…”

“…However, unlike the previous clinical study, we found that pre‐Met administration increased plasma glucose levels at t = 240 min with a delayed peak time compared with post‐Met administration. A possible reason for this late increase in blood glucose levels with a peak delay might be delayed gastric emptying, which we previously reported as a principle mechanism of the TG‐lowering effect of metformin in mice, although the mechanism remains unknown. Several studies have reported that GLP‐1 analogs delay gastric emptying and significantly lower postprandial TG levels in patients with type 2 diabetes mellitus .…”

Metformin does not affect postabsorptive hepatic free fatty acid uptake, oxidation or resecretion in humans: A 3‐month placebo‐controlled clinical trial in patients with type 2 diabetes and healthy controls

“…Although both groups can be considered to be well controlled with regard to glucose homeostasis, it is conceivable that the difference may have resulted in discretely different lipid metabolism before treatment initiation; however, this did not translate into different effects of metformin treatment on lipid metabolism at the end of the study. Third, it is possible that metformin may affect postprandial and not postabsorptive lipid metabolism as suggested by other groups . Exploring this possibility will require a completely different experimental setup.…”

Effects of Dietary Blueberry (<i>Vaccinium ashei</i> Reade) Leaves on Mildly Postprandial Hypertriglyceridemia

“…Despite reports from previous studies showing that postprandial glucose decreased due to delayed gastric emptying 45,46 , the relationship between delayed gastric emptying and decreased postprandial TG was unknown until recently. Sato et al reported that the TG-lowering effect of metformin was mediated by delayed gastric emptying for the first time 47 . In the present study, fasting ghrelin level was extremely correlated with the postprandial TG response, such that the TG-lowering effect of BL was remarkable in subjects with high fasting ghrelin.…”