Impact of Physical Activity and Metformin on Postprandial Glucose

Physical activity and metformin are the first-line treatments for type 2 diabetes; does one have greater impact on quality of life?

The first-line treatment for controlling diabetes starts with lifestyle modifications, including diet, exercise, and weight control. Lifestyle interventions can reduce risk factors for macrovascular and microvascular comorbidities of diabetes. The purpose of this study was to assess the interface of physical activity and metformin as it relates to postprandial glucose in glucose-intolerant people. Studies reported preventing the progression of prediabetes from type 2 diabetes with lifestyle modifications. One study reported a 58% reduction in type 2 diabetes with lifestyle intervention, compared to metformin treatment showing a 31% reduction. However, there have been different outcomes seen with physical activity and metformin for glucose control.   

This study’s objective was to perform a randomized control trial to evaluate the interaction between metformin and exercise training on postprandial glucose and glucose kinetics. The study’s aim was parallel-group, double-blinded. The study designer randomized the study participants into one of two groups; placebo + exercise training (PLA) or metformin + exercise training (MET).  The primary outcome includes postprandial glucose changes measured by the mean glucose concentration during a 4-hour mixed meal tolerance test (MMTT). Participants were included in the study if they had impaired glucose tolerance (7.8-11.0 mmol/L) and A1c of 5.7-6.5% and were glucose-lowering medication naïve, type 2 diabetes patients age 18-70 years old.   

Statistical analysis was determined using the per-protocol, which included all the participants that completed the trial—measuring the group difference using two-way repeated-measures ANOVA for dependent variables, bonferroni-corrected used for within-group differences 95% CIs and p-values, and a two-tailed student’s t-test calculates the outcomes at different time points.   

Fourteen participants completed the MET group and fifteen in the PLA group. Exercise training included 48 sessions for each participant. All participants were compliant PLA 98.5 ± 5.4% vs. MET 97.8 ± 8.1%; p-value of 0.8.  Baseline to training in both groups PLA and MET reported improved postprandial glucose (change in PLA arm -0.7[95% CI -1.4, 0.0] mmol/L, p-value 0.05. Change in MET arm -0.7[-1.5, -0.0] mmol/L, p-value 0.03. Reduction observed from Medication to Training (-0.8 [-1.3, -0.1] mmol/L, p-value 0.01). The MET group had a reduction from Baseline to Medication (-0.9 [-1.6, -0.2] mmol/L, p-value 0.01; mean glucose reductions from Baseline to Training depending on the differential time effects. The PLA group reported a decrease at a time point of 120 min p-value 0.009 compared to MET group reduction seen at a 30 min p-value < 0.001.  Physical fitness was measured using the VO2peak, increased by an average of 15% (4.6 [95% CI 3.3, 5.9] ml/kg/min, p-value < 0.0001 from the Medication to Training.  Bodyweight composition decreased by an average of 4.0 [95% CI -5.2, -2.7] kg, p-value < 0.0001 from Baseline to Training (change in the PLA -3.6 [-5.8, -1.3] kg and change in MET -4.4 [-7.1, -1.7] kg, p-value 0.5. Total fat mass decreased in both groups with a p-value < 0.001.  A1c reduction in the MET group from baseline to training p-value 0.01.  There were no changes reported for fasting glucose in the PLA group. The MET group significantly decreased from Baseline to Training p-value 0.03 and Baseline to Medication p-value <0.0001.   

To conclude, the study hypothesis was determined and proven that metformin plus exercise training is not superior to exercise training alone for improvement in postprandial glucose, as seen in glucose-intolerant individuals. This study’s limitations were the small sample size, which could lead to type 1 and type 2 statistical errors. The authors suggest that future studies are needed to evaluate the interaction of metformin and exercise training, as current guidelines recommend both for first-line treatment options for type 2 diabetes patients.   

Practice Pearls: 

• Lifestyle intervention of physical activity provides an impact on hyperglycemic control. 

• Metformin, along with physical activity, has been the hallmark of recommendations for glycemic control. 
• Physical exercise plays a crucial role in type 2 diabetes management.  

Pilmark, N.S., Lyngbæk, M., Oberholzer, L. et al. The interaction between metformin and physical activity on postprandial glucose and glucose kinetics: a randomized, clinical trial. Diabetologia (2020). https://doi.org/10.1007/s00125-020-05282-6 

Tarshay Boyd, PharmD. Candidate, LECOM School of Pharmacy