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When To Use Metformin

May 18, 2019
 

Author: Steve Freed, R.PH., CDE


Research helps clarify when to use metformin and which groups get the most benefit in diabetes prevention.

There have been many studies on the use of metformin for treating and preventing type 2 diabetes.  Now we have the results on the effects of metformin on diabetes prevention on subgroups that benefited the most over 15 years in the Diabetes Prevention Program (DPP) and the Diabetes Prevention Program Outcomes Study (DPPOS).

 

Over the years we have seen that the longer we can delay the diagnosis of diabetes we can help to prevent the complications from diabetes. But with any drug there are always concerns, regarding its use over a long period of time, as to just how safe it is to use in patients who have prediabetes.

The studies have shown us that the best way to prevent type 2 diabetes is with changing lifestyles and improving our nutrition.  But studies have also shown us that it is very difficult to get patients to improve their lifestyles.

The results from this study can make us feel better about not just telling our patients with prediabetes to change their lifestyles and come back in 3-6 months.  By explaining their risks and how to prevent from getting diabetes for maybe up to 15 years, and explaining the other benefits of using metformin along with changing lifestyles, we could prevent most of the 100 million people in the U.S with prediabetes from progressing to the diagnosis of type 2 diabetes.

Imagine telling the patient that for 3 dollars a month, which is the cost for the prescription for metformin, they can prevent from getting type 2 diabetes on average up to 15 years and longer, and explaining to them that metformin also has other benefits.

For this study they examined the effects of metformin on diabetes prevention and the subgroups that benefited most over 15 years in the Diabetes Prevention Program (DPP) and its follow-up, the Diabetes Prevention Program Outcomes Study (DPPOS). For the DPP study, adults at high risk of developing diabetes were randomly assigned to masked placebo (n = 1,082) or metformin 850 mg twice daily (n = 1,073). Participants originally assigned to metformin continued to receive metformin, unmasked, in the DPPOS (2002–present). Ascertainment of diabetes development was based on fasting or 2-h glucose levels after an oral glucose tolerance test or on HbA1c. Reduction in diabetes incidence with metformin was compared with placebo in subgroups by hazard ratio (HR) and rate differences (RDs).

Whether metformin should be used for diabetes prevention requires a careful balance of benefits and risks. The American Diabetes Association has endorsed its use for this purpose, recommending that “metformin therapy for prevention of type 2 diabetes should be considered in those with prediabetes, especially for those with BMI ≥35 kg/m2, those aged <60 years, women with prior gestational diabetes mellitus, and/or those with rising A1C despite lifestyle intervention.”

The results from this current study of 15 years of post-randomization follow-up showed that metformin reduced the incidence (by Hazard Ratio [HR]) of diabetes compared to placebo by 17% or 36% based on glucose or HbA1c levels, respectively. Metformin’s effect on the development of glucose-defined diabetes was greater for women with a history of prior gestational diabetes mellitus (GDM) compared with women without GDM. Metformin also had greater effects, by HR(Hazard Ratio) and RD(Rate Differences), at higher baseline fasting glucose levels. With diabetes development based on HbA1c, metformin was more effective in subjects with higher baseline HbA1c by RD, with metformin RD −1.03 cases/100 person-years with baseline HbA1c<6.0% (42 mmol/mol) and −3.88 cases/100 person-years with 6.0–6.4% (P = 0.0001).

In summary, regardless of the means by which diabetes is diagnosed, the long-term effects of metformin on diabetes development in DPP/DPPOS suggest that metformin remains effective in this cohort in reducing the development of diabetes over 15 years.  The subsets that benefitted the most include subjects with higher baseline fasting glucose or HbA1c and women with a history of GDM.

Practice Pearls

  • Metformin can be a first option for patients at risk for diabetes.
  • Preventing diabetes for 15 years will reduce the risk for complications.
  • Preventing diabetes and preventing its complications for three dollars a month is a wise investment in our patients’ health.

Diabetes Care 2019 Apr; 42(4): 601-608.https://doi.org/10.2337/dc18-1970