Metformin treatment and gastrointestinal symptoms in youth: Findings from a large tertiary care referral center

Abstract

Objectives Metformin is the only oral therapy for youth with type 2 diabetes, but up to 50% require additional agents within 2 years of diagnosis. Extended‐release (XR) metformin formulations may improve adherence and tolerability–important mediators of treatment response–but data in youth is lacking. To evaluate rates of gastrointestinal (GI) symptoms in patients treated with metformin (SR and XR) and the change in GI symptoms after changes in metformin therapy. Research Design and Methods Retrospective chart review of youth with Type 2 or prediabetes seen in a multidisciplinary clinic during 2016–2019. Results Of 488 eligible patients, 41.4% and 21.1% were taking metformin SR and XR respectively, with most (58%, n = 178/305) taking a total daily dose of ≥1500 mg/day. Those not on metformin tended to be younger, leaner, and had lower HbA1cs than those taking metformin, p < 0.05. Thirty percentage of patients described GI symptoms, most commonly, abdominal pain and diarrhea. There was no difference in GI symptoms in those on SR versus XR (18.3% vs. 14.6%, p = 0.41). Among patients who initiated metformin, rates of GI symptoms increased (13%–33%, p = 0.001, n = 99), while rates tended to decrease when metformin was discontinued (28%–12%, p = 0.076, n = 50). Rates of GI symptoms were unchanged among those that switched from SR to XR metformin (17% vs. 14%, p = 0.6, n = 58). Conclusions GI symptoms are common in youth with type 2 diabetes taking metformin XR and SR. Adjuncts to mitigate GI symptoms in youth on metformin therapy are needed to improve quality of life and medication adherence.

The effects of prebiotics on gastrointestinal side effects of metformin in youth: A pilot randomized control trial in youth-onset type 2 diabetes

“…Our findings are consistent with studies in adults supporting prebiotics as adjunctive therapy in adults on metformin pharmacotherapy (21) (22). This study provided the proof-of-concept needed to further explore prebiotic dietary supplements as adjunctive management with metformin in a vulnerable population of youth with T2DM who have high rates of metformin failure associated with GI symptoms (5).…”

“…Reduced treatment adherence may be multifactorial and is a well-recognized and potentially modifiable risk factor of non-responsiveness (2,3). We and others have shown that medication-related gastrointestinal (GI) side effects (bloating, diarrhea, cramping, nausea, and vomiting) are a common barrier to metformin adherence and maximal dose escalation (4,5). Side effects are observed in >80% of individuals newly initiated on metformin and ~10-30% of patients on long-term therapy with estimates of 1 in 4 youth taking metformin experiencing at least one GI side effect (5)(6)(7).…”

“…We and others have shown that medication-related gastrointestinal (GI) side effects (bloating, diarrhea, cramping, nausea, and vomiting) are a common barrier to metformin adherence and maximal dose escalation (4,5). Side effects are observed in >80% of individuals newly initiated on metformin and ~10-30% of patients on long-term therapy with estimates of 1 in 4 youth taking metformin experiencing at least one GI side effect (5)(6)(7). Challenges are magnified in youth-onset T2DM (Y-T2DM), as metformin is the only oral medication that is approved for use in the 10-17 year age group and age-related factors, including pubertal-related differences in medication responsiveness and microbial signatures, may play a role in the elevated risk (8).…”

Precision therapy for three Chinese families with maturity-onset diabetes of the young (MODY12)

“…At present, very limited types of drugs exist for the treatment of childhood diabetes. Metformin is the only oral therapy for youth with type 2 diabetes, even though up to 50% require additional agents within two years of diagnosis ( 23 ). Therefore, the current status of available treatments for children with type 2 diabetes is not optimistic.…”