Determining which patients benefit most from lifestyle, metformin interventions may improve individualized care decisions.
In a prior study, the Diabetes Prevention Program (DPP), the effect of lifestyle, metformin, and placebo interventions were evaluated on a large population with impaired glucose tolerance. This randomized, controlled trial, proved that lifestyle and metformin interventions were successful in delaying and preventing type 2 diabetes mellitus (DM). However, this study was too broad, making it difficult to understand which patients would gain the most benefit from these interventions. The DPP along with other past studies have failed to measure adherence and risk of both DM development and reversion to normal glucose regulation (NGR).
A recent study was conducted using the study population from the DPP to assess the risk of adherent individuals to develop DM and to revert to NGR over a time period of 3 years. There were 3,234 participants who were over the age of 25 years of age with high pre-prandial blood sugar, with obesity or overweight, had impaired glucose tolerance, and were randomized in the DPP. Of these, 1,079 were placed in the lifestyle modification group, 1,073 were placed in the metformin therapy group, and 1,082 were placed in the placebo group. Nineteen candidate baseline characteristics from the DPP known to be related to DM development and reversion to NGR were utilized to develop Cox proportional hazard models for each intervention group to aid in assessing risk.
Results show that in individuals with the lowest risk of developing DM and who modified their lifestyles, there was a 4% risk of developing DM and an absolute risk reduction (ARR) of 8% when compared to the placebo group. Individuals in the lowest risk group who were used metformin therapy had an 11% risk of developing DM and an ARR of 0% when compared to the placebo group. Those in the lowest risk group who were on placebo therapy had a 12% risk of developing DM. Individuals in the highest risk group of developing DM and who modified their lifestyles had a 19% risk of developing DM and an ARR of 39% when compared to the placebo group. Those in the highest risk group who used metformin therapy has a 34% risk of developing DM and an ARR of 25% when compared to the placebo group. In the highest risk group, those who used placebo therapy had a 59% risk of developing DM.
In addition, individuals with lowest risk who modified their lifestyles had a 35% higher chance of reversion to NGR compared to placebo. Participants in the low risk group who used metformin therapy had a 17% higher chance of reversion to NGR compared to placebo. Individuals in the high risk group who modified their lifestyles had a 24% higher chance of reversion to NGR compared to placebo. And finally, those in the high-risk group who used metformin therapy had an 11% higher chance of reversion to NGR.
According to results, lifestyle interventions are more effective in both low- and high-risk patients at reducing risk of developing DM compared to metformin use alone. The study also shows that metformin therapy is only effective at reducing risk of developing DM in high-risk patients. It was also found that low-risk and high-risk patients in the lifestyle intervention groups had a higher possibility of reverting to NGR when compared to low-risk and high-risk patients on the metformin intervention.
There were limitations to this study, however. Risk equations used were generalized to only the U.S. population who met inclusion criteria for the DPP. Also, participants in the DPP study may have been more dedicated and adherent to interventions in comparison to the general population. It should also be taken into consideration that current DM prevention interventions may differ from the ones used in the DPP.
This study showed how lifestyle modification can lower the risk of getting diabetes and even reverse diabetes compared to just using metformin. But, that brings up the question, what if we combine metformin along with lifestyle modification?
- All patients with obesity or overweight and who are at risk of developing diabetes may benefit more from lifestyle interventions alone versus only using metformin therapy.
- Patients who are at higher risk of developing diabetes may benefit more from metformin
- Determining 3-year risk for diabetes development and reversion to normal glucose regulation can help patients modify their treatment plans, making them more successful and cost-effective.
Herman WH, Pan Q, Edelstein SL, et al. Impact of Lifestyle and Metformin Interventions on the Risk of Progression to Diabetes and Regression to Normal Glucose Regulation in Overweight or Obese People With Impaired Glucose Regulation. Diabetes Care. 2017; 0: 1-10.
Graciela Nieto, Pharm. D. Candidate 2018, LECOM School of Pharmacy