4. Drug-Drug Interactions
Patient profiles will be assessed to identify those drug regimens, which may result in clinically significant drug-drug interactions. Drug-drug interactions considered clinically relevant for GLP-1 agonists are summarized in Table 2. Only those drug-drug interactions identified as clinical significance level 1 or those considered life-threatening which have not yet been classified will be reviewed.
| Target Drug | Interacting Drug | Interaction | Recommendation | Clinical Significance Level* |
|---|---|---|---|---|
| antidiabetic agents | fluoroquinolones | adjunctive administration may result in blood glucose disturbances and increased risk for hyper- or hypoglycemia due to an unknown mechanism | closely monitor blood glucose levels and adjust antidiabetic doses as needed; doses may also require adjustments with fluoroquinolone discontinuation | major (DrugReax) 3-moderate (CP) |
| antidiabetic agents | somatostatin analogues (SAs) (e.g., octreotide, pasireotide) | concurrent use may impair glucose regulation as SAs inhibit insulin and glucagon secretion; substantially increased blood glucose levels may result | monitor closely for changes in blood glucose control before and throughout SA therapy; adjust antidiabetic doses as needed | major (DrugReax) 2-major (CP) |
| exenatide, semaglutide, lixisenatide, tirzepatide | warfarin | concurrent administration may result in increased international normalized ratio (INR), sometimes with associated bleeding; mechanism unknown | closely monitor for changes in INR and bleeding with exenatide/warfarin drug combination | moderate (DrugReax) 3-moderate (CP) |
| GLP-1 agonists | gastric stimulants (e.g., metoclopramide, tegaserod) | concurrent administration may attenuate pharmacologic effects due to competing effects from both agents | monitor blood glucose levels and adjust antidiabetic doses as needed | 3-moderate (CP) |
| GLP-1 agonists | insulin secretagogues (e.g., sulfonylureas, insulin) | adjunctive administration may lead to increased hypoglycemia due to additive glucose-lowering effects | avoid use, if possible; if combined use needed, adjust insulin secretagogue or insulin doses and closely monitor blood glucose levels | major, moderate (DrugReax) 2-major, 3-moderate (C)P) |
| GLP-1 agonists | oral contraceptives (OCs) | concurrent administration may reduce OC serum levels and reduce efficacy as GLP-1 agonists delay gastric emptying; also, estrogens and progestins impair glucose tolerance | use cautiously together; administer OCs at least 1 hour before GLP-1 agonists and monitor for glycemic control | lixisenatide – major (DrugReax) 3-moderate (CP) |
| tirzepatide | oral contraceptives (OCs) | concurrent administration may reduce OC serum levels and reduce efficacy as GIP/GLP-1 agonists delay gastric emptying; the impact the greatest after the first dose, and this effect diminishes with subsequent doses | use non-oral contraceptive or add barrier method for the 4 weeks after initiation and 4 weeks after each dose escalation | 2-major (CP) |
| GLP-1 agonists | oral medications with hypoglycemic effects (e.g., oral antidiabetic agents, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, fibric acid derivatives, salicylates, sulfonamide antibiotics) | concomitant administration may result in enhanced hypoglycemic pharmacologic and adverse effects | monitor blood glucose levels closely and adjust dosages as necessary if drug combination required to minimize excessive hypoglycemia and associated adverse events | 3-moderate (CP) |
| GLP-1 agonists | oral medications that slow gastrointestinal motility (e.g., opiate agonists, tricyclic antidepressants, antimuscarinics, diphenoxylate) | adjunctive administration may potentiate GLP-1 agonist pharmacologic effects, including additional blood glucose reductions and hypoglycemia risk | use cautiously together | undetermined |
Legend:
- *CP = Clinical Pharmacology