3.0.0.0 PHAR­MA­CO­LOG­IC IN­TER­VEN­TIONS

Rec­om­men­da­tions

3.5 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, and women with prior ges­ta­tion­al di­a­betes mel­li­tus. A

3.6 Long-‍term use of met­formin may be as­so­ci­at­ed with bio­chem­i­cal vi­ta­min B12 deficien­cy, and pe­ri­od­ic mea­sure­ment of vi­ta­min B12 lev­els should be con­sid­ered in met­formin-‍treat­ed pa­tients, es­pe­cial­ly in those with ane­mia or pe­riph­er­al neu­ropa­thy. B

Phar­ma­co­log­ic agents in­clud­ing met­formin, α-‍glu­cosi­dase in­hibitors, glucagon-‍like pep­tide 1 re­cep­tor ag­o­nists, thi­a­zo­lidine­diones, and sev­er­al agents ap­proved for weight loss have been shown in re­search stud­ies to de­crease the in­ci­dence of di­a­betes to var­i­ous de­grees in those with predi­a­betes (1,43–49), though none are ap­proved by the U.S. Food and Drug Ad­min­is­tra­tion specifically for di­a­betes pre­ven­tion. One has to bal­ance the risk/ benefit of each med­i­ca­tion. Met­formin has the strongest ev­i­dence base (50) and demon­strated long-‍term safe­ty as phar­ma­co­log­ic ther­a­py for di­a­betes pre­ven­tion (48). For other drugs, cost, side ef­fects, and durable efficacy re­quire con­sid­er­a­tion.

Met­formin was over­all less ef­fec­tive than lifestyle modification in the DPP and DPPOS, though group dif­fer­ences de­clined over time (5) and met­formin may be cost-‍sav­ing over a 10-year pe­ri­od (34). It was as ef­fec­tive as lifestyle modification in par­tic­i­pants with BMI ≥35 kg/m2 but not significant­ly bet­ter than place­bo in those over 60 years of age (1). In the DPP, for women with his­to­ry of GDM, met­formin and in­ten­sive lifestyle modification led to an equiv­a­lent 50% re­duc­tion in di­a­betes risk (51), and both in­ter­ven­tions re­mained high­ly ef­fec­tive dur­ing a 10-year fol­low-‍up pe­ri­od (52). In the In­di­an Di­a­betes Pre­ven­tion Pro­gramme (IDPP-1), met­formin and the lifestyle in­ter­ven­tion re­duced di­a­betes risk sim­i­larly at 30 months; of note, the lifestyle in­ter­ven­tion in IDPP-1 was less in­ten­sive than that in the DPP (53). Based on find­ings from the DPP, met­formin should be rec­om­mend­ed as an op­tion for high-‍risk in­di­vid­u­als (e.g., those with a his­to­ry of GDM or those with BMI ≥35 kg/m2). Con­sid­er mon­i­tor­ing vi­ta­min B12 lev­els in those tak­ing met­formin chron­i­cal­ly to check for pos­si­ble deficien­cy (54) (see Sec­tion 9 “Phar­ma­co­log­ic Ap­proach­es to Glycemic Treat­ment” for more de­tails).