From the Guidelines
DPP-4 inhibitors have the least gastrointestinal side effects among Oral Hypoglycemic Agents (OHAs) [ 1, 2, 3 ].
Key Points
- Gastrointestinal Side Effects: High-quality evidence showed no difference between thiazolidinediones and sulfonylureas for gastrointestinal side effects 1.
- DPP-4 Inhibitors: Moderate-quality evidence indicated that monotherapy with a DPP-4 inhibitor was associated with a lower risk for mild, moderate, or total hypoglycemia than sulfonylureas 1.
- Metformin: Metformin is associated with initial gastrointestinal side effects, and caution is advised to avoid its use in patients at risk for lactic acidosis 2.
- Comparison of OHAs: The combination of metformin and a DPP-4 inhibitor was associated with a lower risk for severe hypoglycemia than metformin plus a sulfonylurea 1.
Medication Comparison
- DPP-4 Inhibitors: Intermediate glucose-lowering efficacy, no increased risk of hypoglycemia, neutral weight effects, and no dose adjustment required for linagliptin 3.
- Metformin: High glucose-lowering efficacy, no increased risk of hypoglycemia, neutral weight effects, and potential benefits for cardiovascular events and mortality 4, 3.
- Sulfonylureas: High glucose-lowering efficacy, increased risk of hypoglycemia, weight gain, and neutral effects on cardiovascular events 2, 3.
From the Research
Oral Hypoglycemic Agents (OHAs) and Gastrointestinal Side Effects
The available evidence suggests that different OHAs have varying levels of gastrointestinal side effects.
- Metformin is associated with chronic diarrhea and fecal incontinence, as reported in a study published in 2001 5.
- Sulphonylureas are not associated with significant gastrointestinal symptoms, except for less abdominal pain 5.
- Dipeptidyl peptidase-IV (DPP-4) inhibitors have a low side-effect profile, including gastrointestinal side effects, making them a recommended alternative when metformin use is limited by gastrointestinal side effects 6.
- Meglitinide analogs and α-glucosidase inhibitors are limited by their dosing schedule and gastrointestinal side-effect profile 6.
- Bile-acid sequestrants and bromocriptine have the lowest efficacy and are plagued by gastrointestinal adverse reactions 6.
Comparison of OHAs
Based on the available evidence, DPP-4 inhibitors appear to have the least gastrointestinal side effects among the OHAs, making them a suitable alternative for patients who experience gastrointestinal side effects with metformin or other OHAs 6.
- The study published in 2001 5 and the review published in 2013 6 provide evidence on the gastrointestinal side effects of different OHAs.
- Other studies, such as those published in 2015 7, 2017 8, and 2019 9, provide additional information on metformin, but do not directly compare the gastrointestinal side effects of different OHAs.