Diabetes In Focus
 

 Metformin adherence could lower polyneuropathy risk

Adherence to metformin significantly reduces the risk of polyneuropathy in patients with type 2 diabetes who require second-line treatment,

according to a study published in Metabolic Syndrome and Related Disorders.

Researchers analyzed data from nearly 360,000 patients and found that those who adhered to metformin had a lower incidence of polyneuropathy

and related complications such as limb amputation and diabetic foot ulcers.

 

The study suggests that long-term metformin use may have neuroprotective effects, and it recommends routine vitamin B12 monitoring for chronic users.

 

 

Metformin Adherence Lowers Polyneuropathy Risk in Type 2 Diabetes

 

Long-term adherence to second-line metformin therapy is associated with a significantly reduced risk for diabetic polyneuropathy and other complications in patients with type 2 diabetes.

Polyneuropathy risk is reduced with metformin adherence among patients with type 2 diabetes mellitus (T2DM) who require second-line treatment. These findings were published in Metabolic Syndrome and Related Disorders.

 

 

Diabetic polyneuropathy presents as stock-and-glove sensory abnormalities with sensations of numbness, paresthesia, and/or pain.

Investigators from Taipei Medical University in Taiwan analyzed data from the TriNetX Global Collaborative Network. Patients (n=359,872) with T2DM who used second-line metformin between 2005 and 2023 were evaluated for new-onset polyneuropathy on the basis of metformin adherence.

 

 

Nonadherence was defined as discontinuation, and adherence was defined as a medication possession ratio (MPR) of at least 40%. To balance for cohort differences, 58,027 individuals without adherence were matched with 58,027 individuals with adherence. Trends were validated using data from the Taiwan National Health Insurance Research Database, comprising matched metformin nonadherent (n=31,384) and adherent (n=31,384) patients with T2DM.

 

 

Routine monitoring and supplementation of vitamin B12 should be considered in chronic metformin users to maintain an optimal benefit–risk balance.

 

 

The prematched nonadherent (n=58,027) and adherent (n=359,872) cohorts, of whom 48.3% and 52.5% men and 58.3% and 45.3% were White, respectively, had mean (SD) ages of 56.8 (12.7) and 57.7 (12.1) years, body mass index (BMI) of 34.9 (8.2) and 33.9 (7.8), and glycated hemoglobin (HbA1c) of 8.6% (2.3%) and 8.1% (2.1%), respectively.

In the matched groups, a total of 13,979 individuals who were nonadherent and 12,467 who were adherent to metformin treatment were diagnosed with polyneuropathy. Individuals who were not adherent to metformin were at higher risk for polyneuropathy (adjusted hazard ratio [aHR], 1.26; 95% CI, 1.23-1.29; P <.0001).

Metformin nonadherence was also associated with risks for limb or toe amputation (aHR, 1.70; 95% CI, 1.54-1.87; P <.0001), diabetic foot ulcer (aHR, 1.30; 95% CI, 1.25-1.35; P <.0001), polyneuropathy medication use (aHR, 1.18; 95% CI, 1.16-1.20; P <.0001), and bone fracture (aHR, 1.12; 95% CI, 1.08-1.16; P <.0001).

 

 

In the subgroup analyses, nonadherence to metformin was associated with increased risk for polyneuropathy, diabetic foot ulcer, and limb or toe amputation across subgroups, except among individuals who used vitamin B supplements (aHR range, 0.80-1.04).

 

 

In the sensitivity analyses, metformin nonadherence was associated with increased risk for polyneuropathy when excluding events in the first 24 (aHR, 1.26; 95% CI, 1.23-1.29; P <.0001), 36 (aHR, 1.26; 95% CI, 1.22-1.29; P <.0001), 48 (aHR, 1.26; 95% CI, 1.22-1.29; P <.0001), or 60 (aHR, 1.27; 95% CI, 1.23-1.31; P <.0001) months.

 

 

The relationship between metformin nonadherence and polyneuropathy risk was validated using the Taiwan database (aHR, 1.25; 95% CI, 1.10-1.42; P <.001).

This study was limited by lack of access to potentially relevant lifestyle factors.

 

 

The study investigators concluded, “[O]ur results demonstrate that long-term adherence to metformin is associated with a substantially reduced risk of diabetic polyneuropathy across independent, large-scale cohorts. This association persisted after rigorous adjustment and validation, suggesting that sustained metformin use — among patients who tolerate it well — may confer clinically meaningful neuroprotective effects. Routine monitoring and supplementation of vitamin B12 should be considered in chronic metformin users to maintain an optimal benefit–risk balance.”
 

 

 

Nyhetsinfo

www red DiabetologNytt