From the Guidelines
For a newly diagnosed type 2 diabetic patient who cannot tolerate metformin due to diarrhea, a sodium-glucose cotransporter-2 (SGLT2) inhibitor or a glucagon-like peptide-1 (GLP-1) receptor agonist would be the most appropriate next-line options. These classes of medications have been shown to provide significant benefits in terms of glycemic control, cardiovascular risk reduction, and weight management 1. SGLT2 inhibitors, such as empagliflozin (10-25 mg daily), dapagliflozin (5-10 mg daily), or canagliflozin (100-300 mg daily), work by preventing glucose reabsorption in the kidneys, leading to increased urinary glucose excretion. GLP-1 receptor agonists, such as semaglutide (0.25-1 mg weekly injection or 3-14 mg oral daily), dulaglutide (0.75-4.5 mg weekly injection), or liraglutide (0.6-1.8 mg daily injection), stimulate insulin secretion, suppress glucagon, and slow gastric emptying, promoting weight loss and cardiovascular benefits.
Key considerations in choosing between these options include:
- Cardiovascular risk: SGLT2 inhibitors have demonstrated significant cardiovascular benefits, including reduced risk of heart failure and renal disease 1.
- Renal function: SGLT2 inhibitors may be preferred in patients with impaired renal function, as they have been shown to slow the progression of kidney disease 1.
- Weight management goals: GLP-1 receptor agonists may be preferred in patients with significant weight loss goals, as they promote weight loss and improve glycemic control 1.
- Preference for oral versus injectable therapy: SGLT2 inhibitors are available in oral formulations, while GLP-1 receptor agonists are available in both oral and injectable formulations.
Other options, such as DPP-4 inhibitors like sitagliptin (100 mg daily), may also be considered, although they may have more modest glucose-lowering effects compared to SGLT2 inhibitors and GLP-1 receptor agonists 1. Regular monitoring of blood glucose, kidney function, and potential side effects is essential with any of these alternatives. According to the American Diabetes Association standards of medical care in diabetes, a patient-centered approach should be used to guide the choice of pharmacologic agents 1.
From the FDA Drug Label
For patients who had not been previously treated with antidiabetic medication (40%), mean values at screening were 10. 3% for HbA1c and 240 mg/dL for FPG. The next treatment option for a newly diagnosed type 2 diabetic patient with diarrhea who cannot tolerate metformin is pioglitazone (PO), as it has been shown to reduce HbA1c and FPG levels in patients with type 2 diabetes, including those who are treatment-naive 2.
- Key benefits of pioglitazone include:
- Reductions in mean HbA1c of 1.0% and mean FPG of 62 mg/dL compared to placebo
- Therapeutic effect observed regardless of prior treatment status However, it is essential to consider the patient's individual needs and medical history before initiating treatment with pioglitazone.
From the Research
Next Treatment Options for Type 2 Diabetes
When a patient is unable to tolerate metformin due to diarrhea, several alternative treatment options can be considered.
- DPP-4 Inhibitors: Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is a potential next option 3, 4. It works by increasing the amount of circulating incretins, which stimulate insulin secretion and inhibit glucose production. Sitagliptin can be used alone or in combination with other antidiabetic agents.
- Alternative Antidiabetic Agents: If metformin is contraindicated or not tolerated, other classes of agents can be used to treat hyperglycemia associated with type 2 diabetes mellitus 5. The choice of agent depends on various factors, including efficacy, adverse effect profile, cost, and patient preference.
- Combination Therapy: Fixed-dose combination treatment with sitagliptin and metformin is also an option, but may not be suitable for patients who cannot tolerate metformin 6. In such cases, sitagliptin can be used as monotherapy or in combination with other antidiabetic agents.
Considerations for Treatment Selection
When selecting an alternative treatment option, the following factors should be considered: