The effects of metformin and glibenclamide on glucose metabolism, counter‐regulatory hormones and cardiovascular responses in women with Type 2 diabetes during exercise of moderate intensity

Cunha, M. R.; Silva, M. E. R. Da; Machado, H. A.; Fukui, Rosa Tsunechiro; Correa, Mariangela; Santos, R. F.; Wajchenberg, B. L.; Rondon, M. U. P. B.; Negräo, Carlos Eduardo; Ursich, Mileni Josefina Maria

doi:10.1111/j.1464-5491.2007.02117.x

Cited by 10 publications

(11 citation statements)

References 45 publications

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“…We are aware of nonexercise studies that have suggested that metformin may increase glucagon concentrations, but the increases were not statistically significant (24,25). In the nonrandomized exercise studies by Cunha et al (14,15), glucagon concentrations were significantly higher in the participants with type 2 diabetes taking metformin compared with those taking glibenclamide or those with normal glucose tolerance. Although speculative, the glucose-lowering benefits of metformin could be further enhanced by strategies that could help minimize the exercise-induced increased glucagon levels such as exercising after a meal.…”

Section: Discussionmentioning

confidence: 90%

“…Although the combination of metformin and exercise was perceived as safe, interest in this area has reemerged in recent years (4,7,14,15). The current study is unique in that it focused on continuous exercise at several submaximal intensities that are relevant to activity patterns of people with type 2 diabetes and that we examined the interaction between exercise and metformin on the glycemic and hormonal responses to a subsequent meal.…”

Section: Discussionmentioning

confidence: 99%

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Metformin and Exercise in Type 2 Diabetes

et al. 2011

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OBJECTIVETo determine the effect of metformin on the acute metabolic response to submaximal exercise, the effect of exercise on plasma metformin concentrations, and the interaction between metformin and exercise on the subsequent response to a standardized meal.RESEARCH DESIGN AND METHODSTen participants with type 2 diabetes were recruited for this randomized crossover study. Metformin or placebo was given for 28 days, followed by the alternate condition for 28 days. On the last 2 days of each condition, participants were assessed during a nonexercise and a subsequent exercise day. Exercise took place in the morning and involved a total of 35 min performed at three different submaximal intensities.RESULTSMetformin increased heart rate and plasma lactate during exercise (both P ≤ 0.01) but lowered respiratory exchange ratio (P = 0.03) without affecting total energy expenditure, which suggests increased fat oxidation. Metformin plasma concentrations were greater at several, but not all, time points on the exercise day compared with the nonexercise day. The glycemic response to a standardized meal was reduced by metformin, but the reduction was attenuated when exercise was added (metformin × exercise interaction, P = 0.05). Glucagon levels were highest in the combined exercise and metformin condition.CONCLUSIONSThis study reveals several ways by which metformin and exercise therapies can affect each other. By increasing heart rate, metformin could lead to the prescription of lower exercise workloads. Furthermore, under the tested conditions, exercise interfered with the glucose-lowering effect of metformin.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Metformin and Exercise in Type 2 Diabetes

et al. 2011

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“…We evaluated whether this might influence our findings because sulfonylureas have been reported to influence oxygen consumption at rest in swine (Duncker et al 1993). However, there is no evidence that sulfonylureas affect exercise capacity in humans or swine (Duncker et al 1993;Cunha et al 2007). Importantly, we found no differences in echocardiographic function at rest or _ V O 2 peak between T2D subjects who were taking sulfonylureas and T2D subjects who were not taking sulfonylureas (Regensteiner et al 1998).…”

Section: Fig 1 (A)mentioning

confidence: 92%

“…Subjects taking prescription medications other than oral sulfonylureas were excluded for the purpose of consistency and to avoid potential confounding effects of medication on peak exercise capacity, which was the primary outcome in the original study for which we collected these data. Sulfonylureas do not appear to influence physiological factors related to peak exercise capacity, based on limited existing data in animals (Duncker et al 1993) and humans (Cunha et al 2007). Eight subjects with T2D were taking sulfonylureas (n = 6, glyburide; n = 2, glipizide).…”

Section: Participantsmentioning

confidence: 95%

Women with type 2 diabetes perceive harder effort during exercise than nondiabetic women

Huebschmann

Reis

Emsermann

et al. 2009

Appl. Physiol. Nutr. Metab.

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Regular exercise is a cornerstone of diabetes treatment; however, people with type 2 diabetes (T2D) are commonly sedentary. It is possible that a harder rate of perceived exertion (RPE) during exercise for those with T2D as compared with nondiabetics may be a barrier to physical activity. This study examined RPE (Borg scale, ordinal range 6-20) during submaximal exercise at identical absolute work rates to test the hypothesis that women with T2D demonstrate harder RPE during exercise than nondiabetic controls. In a prespecified analysis of existing data from equivalently sedentary women, RPE during submaximal exercise was compared among women with uncomplicated T2D (n = 13, mean body mass index (BMI) 34.2, mean hemoglobin A1c 9%), overweight controls (OC, n = 13, mean BMI 30.7), and normal-weight controls (NWC, n = 13, mean BMI 23.1). Subjects performed three 7 min, constant-load exercise tests at 20 W and 30 W. Mixed-effects general linear modeling was used to test for differences in mean RPE estimates among groups with and without adjustment for relative work intensity, age, habitual physical activity, or BMI. Subjects with T2D perceived harder effort during bicycling exercise than controls, as measured by RPE at 20 W and 30 W (p < 0.05 for T2D vs. OC and for T2D vs. NWC). Adjusting for relative work intensity eliminated significant group RPE differences at 30 W, but group RPE differences at 20 W remained significant. Harder perceived effort during exercise may be a barrier to physical activity for those with T2D.

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“…Some studies suggest that acute and/or short‐term metformin administration promotes fatigue resistance during high‐intensity exercise, while lowering lactate and facilitating carbohydrate oxidation and glucose homeostasis during standardized exercise . Others have reported that metformin decreases peak oxygen uptake, and increases exercise heart rate and lactate, or has no influence on cardiovascular and endocrine responses to exercise . In vitro data suggest high concentrations of metformin inhibit mitochondrial complex I, however, when experiments utilize concentrations of metformin associated with standard doses, mitochondrial respiration is not impaired .…”

Section: Discussionmentioning

confidence: 99%

Ergogenic properties of metformin in simulated high altitude

Scalzo

Paris

Binns

et al. 2017

Clin Exp Pharma Physio

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Metformin augments glucose/glycogen regulation and may acutely promote fatigue resistance during high-intensity exercise. In hypobaric environments, such as high altitude, the important contribution of carbohydrates to physiological function is accentuated as glucose/glycogen dependence is increased. Because hypoxia/hypobaria decreases insulin sensitivity, replenishing skeletal muscle glycogen in high altitude becomes challenging and subsequent physical performance may be compromised. We hypothesized that in conditions where glycogen repletion was critical to physical outcomes, metformin would attenuate hypoxia-mediated decrements in exercise performance. On three separate randomly ordered occasions, 13 healthy men performed glycogen-depleting exercise and ingested a low-carbohydrate dinner (1200 kcals, <10% carbohydrate). The next morning, in either normoxia or hypoxia (FiO =0.15), they ingested a high-carbohydrate breakfast (1225 kcals, 70% carbohydrate). Placebo (719 mg maltodextrin) or metformin (500 mg BID) was consumed 3 days prior to each hypoxia visit. Subjects completed a 12.5 km cycle ergometer time trial 3.5 hours following breakfast. Hypoxia decreased resting and exercise oxyhemoglobin saturation (P<.001). Neither hypoxia nor metformin affected the glucose response to breakfast (P=.977), however, compared with placebo, metformin lowered insulin concentration in hypoxia 45 minutes after breakfast (64.1±6.6 μU/mL vs 48.5±7.8 μU/mL; mean±SE; P<.001). Post-breakfast, pre-exercise vastus lateralis glycogen content increased in normoxia (+33%: P=.025) and in hypoxia with metformin (+81%; P=.006), but not in hypoxia with placebo (+27%; P=.167). Hypoxia decreased time trial performance compared with normoxia (P<.01). This decrement was similar with placebo (+2.6±0.8 minutes) and metformin (+1.6±0.3 minutes). These results indicate that metformin promotes glycogen synthesis but not endurance exercise performance in healthy men exposed to simulated high altitude.

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The effects of metformin and glibenclamide on glucose metabolism, counter‐regulatory hormones and cardiovascular responses in women with Type 2 diabetes during exercise of moderate intensity

Cited by 10 publications

References 45 publications

Metformin and Exercise in Type 2 Diabetes

Metformin and Exercise in Type 2 Diabetes

Women with type 2 diabetes perceive harder effort during exercise than nondiabetic women

Ergogenic properties of metformin in simulated high altitude

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