Artificial sweeteners may reduce metformin’s effectiveness in weight and glucose control

Can sugar-free drinks make diabetes treatment less effective? A new study suggests artificially sweetened beverages might blunt metformin’s benefits, raising questions about their impact on weight loss and insulin resistance.

Study: The Impact of Artificially Sweetened Drinks on Metformin Efficacy. Image Credit: VTT Studio / Shutterstock

Recent estimates suggest that 20% of American children suffer from pediatric obesity, increasing the risk of adult obesity and several chronic diseases, while type 2 diabetes (T2D) and prediabetes in this age group also continue to rise. Childhood obesity has been linked to poorer health and higher mortality in the long term, even for individuals who lose excess weight in adulthood.

The popularity of sugar-sweetened beverages (SSBs) has also increased sharply. SSB consumption has been linked to obesity. Individuals, including children, who consume more SSBs are also more likely to develop heart disease, T2D, metabolic syndrome, and insulin resistance.

In recent years, there has been a rise in the use of non-nutritive or artificial sweeteners (NNS); the ASBs containing these sweeteners are advertised as healthier than SSBs since they have little to no caloric content. Initial studies suggested that these ASBs had no metabolic effects, but recent research indicates that NNS may reduce gut health and disrupt the systems that control satiety, causing weight gain, impaired tolerance to glucose, and worsened heart health.

This raises concerns about whether ASBs may impair the efficacy of diabetes medications such as metformin, which is a safe and affordable drug commonly used to treat pediatric T2D.

Metformin has moderate, if inconsistent, weight loss effects. It also reduces metabolic complications related to obesity and is thought to improve gut microbiome health. Separately, metformin increases levels of growth differentiation factor 15 (GDF-15), which regulates body weight, food intake, and energy expenditure, as well as activating adenosine monophosphate-activated protein kinase (AMPK), another important metabolism regulator.

Recent mouse models show that ASB consumption can reduce the efficacy of metformin in promoting glucose control and weight loss, but similar studies have not been conducted for humans.

About the Study

Researchers recruited eligible participants from a Florida clinic using chart reviews and preclinical screening to receive a 12-week metformin intervention. The 46 participants were between the ages of 10 and 21 and had been diagnosed with obesity and prediabetes. Individuals who had hypertension or received drugs to help control blood sugar levels were excluded, as were those who were pregnant.

Participants were told to drink at least three beverages a day, but half were randomly selected for the ASB group – this group was instructed to drink ASBs while the others were told to avoid sweetened beverages. At baseline, the research team assessed their eating behaviors and physical health, including weight and height; laboratory tests were used to collect information about their fasting GDF-15, hemoglobin, insulin, and glucose.

Throughout the intervention, participants submitted bi-weekly reports with information about their beverage intake. After 12 weeks, fasting data and information on metformin compliance, hunger, and eating behavior were collected again. The analysis involved generating frequency distributions and measures of central tendency and dispersion before using statistical tests to compare the two groups (ASB and comparison).

Findings

More than 54% of the participants were female; 25 out of 46 identified as Black or African American, while 41 were non-Latino or non-Hispanic. Before the intervention, 30.4% said they occasionally felt hungry, 45.7% reported sometimes asking for second servings after their meals, and 87% reported snacking between meals.

Of the 46 enrolled participants, 36 completed the program, including 44% from the control group. This group, who did not consume ASBs, showed more significant declines in BMI and larger increases in levels of GDF-15 than those who consumed ASBs, though these differences were not statistically significant (p = 0.6 for GDF-15; p = 0.53 for BMI). Researchers found no changes in dietary intake or hemoglobin.

Notably, in a post-hoc exploratory analysis, 90% of participants in the control group showed decreases in insulin resistance compared to less than 40% of those consuming ASBs, a statistically significant difference (p = 0.0084).

Conclusions

The pilot study results indicate that drinking ASBs may impair the effectiveness of metformin for pediatric patients; GDF-15 may be a possible mediating factor. However, while trends favored the non-ASB group for BMI and GDF-15, the primary outcomes did not reach statistical significance. The significant post-hoc finding for insulin resistance reduction in the control group suggests further investigation is warranted.

The authors also noted that their study population included a large number of African American individuals, which reflects the increased obesity risk that this demographic experiences.

The limited sample size and short duration likely contributed to the lack of statistically significant findings for primary outcomes, highlighting the need for further exploration of the mechanism impacts and pathophysiology of artificial sweeteners on metabolic functioning. Clinical research involving a larger number of participants over a longer period could confirm these findings.