Postprandial hyperglycemia was ameliorated by taking metformin 30 min before a meal than taking metformin with a meal; a randomized, open-label, crossover pilot study

Hashimoto, Yoshitaka; Tanaka, Muhei; Okada, Hiroshi; Mistuhashi, Kazuteru; Kimura, Toshihiro; Kitagawa, Noriyuki; Fukuda, Takuya; Majima, Susumu; Fukuda, Yukiko; Tanaka, Yoshimitsu; Yamada, Shunji; Senmaru, Takafumi; Asano, Mai; Yamazaki, Masahiro; Oda, Y.; Hasegawa, Goji; Nakamura, Naoto; Fukui, Michiaki

doi:10.1007/s12020-015-0786-4

Cited by 12 publications

(13 citation statements)

References 19 publications

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“…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. 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.…”

Section: Discussionsupporting

confidence: 93%

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

Sato

Morino

Ogaku

et al. 2019

J of Diabetes Invest

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Aims/Introduction Preprandial metformin administration significantly reduces postprandial plasma triglyceride levels in animal studies by reducing intestinal absorption through delayed gastric emptying. However, this effect has not been shown in a clinical study. Therefore, we planned to investigate the efficacy of preprandial metformin administration on postprandial hypertriglyceridemia and the related gastrointestinal effects in patients with type 2 diabetes mellitus. Materials and Methods A total of 11 patients taking single‐dose metformin at 500–1,000 mg, with non‐fasting plasma triglyceride levels of 150–1,000 mg/dL, were recruited at a single university hospital. The difference between preprandial and postprandial metformin administration on postprandial hypertriglyceridemia was examined by a meal test. The gastrointestinal effects of metformin, including stomach heaviness, heartburn and satiety, were also assessed using a visual analog scale. Results The mean bodyweight of patients was 80.6 kg (body mass index 27.9 kg/m2), and the mean non‐fasting plasma triglyceride level was 275.9 ± 57.0 mg/dL. The area under the curve of triglyceride during the meal test was significantly lower in the preprandial protocol than in the postprandial protocol (P < 0.05). Compared with postprandial administration, preprandial administration of metformin increased satiety (P = 0.036) without stomach heaviness or heartburn. Conclusions Preprandial metformin administration significantly reduced plasma triglyceride level during meal testing without marked exacerbation of gastrointestinal adverse effects. The present results suggest that a simple change in the timing of metformin administration represents a novel approach for enhancing triglyceride‐lowering strategies in patients with type 2 diabetes mellitus and postprandial hypertriglyceridemia.

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Section: Discussionsupporting

confidence: 93%

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

Sato

Morino

Ogaku

et al. 2019

J of Diabetes Invest

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“…However, post-meal administration of metformin is performed to maintain patients’ adherence in the clinical setting. A recent report revealed that postprandial glucose levels are improved by pre-meal administration of metformin compared with those following post-meal treatment [24]. Our data demonstrated that pre-meal treatment of metformin significantly improved both glucose and TG concentrations compared with post-meal administration (Figure 2C,E).…”

Section: Discussionsupporting

confidence: 64%

Acute Effect of Metformin on Postprandial Hypertriglyceridemia through Delayed Gastric Emptying

Sato

Morino

Nakagawa

et al. 2017

IJMS

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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.

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“…Metformin has been reported to suppress glucose spikes when taken prior to meals [ 25 ]. However, in the present study, metformin was not administered prior to the OGTT.…”

Section: Discussionmentioning

confidence: 99%

<i>Bifidobacterium bifidum</i> G9-1 ameliorates soft feces induced by metformin without affecting its antihyperglycemic action

Makizaki

Maeda

Yamamoto

et al. 2020

Bioscience of Microbiota, Food and Health

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Recent studies of metformin, the first-line drug for type 2 diabetes, have reported the involvement of gut microbiota in the mechanism underlying its antihyperglycemic effect. However, the mechanisms underlying the development of diarrhea and bloating, which are adverse effects of metformin, are unclear, and these effects decrease the quality of life of metformin-receiving patients with diabetes. In this study, we focused on the effects of metformin on gut microbiota. Namely, we examined the effects of Bifidobacterium bifidum G9-1 (BBG9-1), which has the ability to improve dysbiosis, on the changes in gut microbiota and occurrence of soft feces (increased fecal water content) during the administration of metformin. The results showed that coadministration of BBG9-1 and metformin suppressed metformin-mediated changes in the gut microbiota and, thus, soft feces. Meanwhile, BBG9-1 did not influence the antihyperglycemic effect of metformin. Based on these results, we believe that BBG9-1, which could improve gut microbiota, suppresses metformin-induced soft feces without influencing the drug’s antihyperglycemic effect.

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Postprandial hyperglycemia was ameliorated by taking metformin 30 min before a meal than taking metformin with a meal; a randomized, open-label, crossover pilot study

Cited by 12 publications

References 19 publications

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

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

Acute Effect of Metformin on Postprandial Hypertriglyceridemia through Delayed Gastric Emptying

<i>Bifidobacterium bifidum</i> G9-1 ameliorates soft feces induced by metformin without affecting its antihyperglycemic action

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