From the Guidelines
For a 38-year-old with type 2 diabetes currently on metformin 500 mg twice daily and glargine 7 units at night with good glucose control, I recommend adding a sodium-glucose cotransporter-2 (SGLT2) inhibitor such as empagliflozin 10 mg daily or a glucagon-like peptide-1 (GLP-1) receptor agonist like semaglutide 0.25 mg weekly (titrated up to 1 mg weekly over time) while gradually tapering off the glargine insulin. This approach is supported by recent guidelines that suggest the use of SGLT2 inhibitors or GLP-1 receptor agonists as part of combination therapy for patients with type 2 diabetes who are not achieving glycemic targets with metformin alone 1. The choice between an SGLT2 inhibitor and a GLP-1 receptor agonist should be based on patient-specific factors, such as the presence of established cardiovascular disease or indicators of high cardiovascular risk, as well as the patient's preferences and values 1. Key benefits of SGLT2 inhibitors include their ability to increase glucose excretion through the kidneys, providing cardiovascular and renal benefits with weight loss and minimal hypoglycemia risk 1. On the other hand, GLP-1 receptor agonists enhance insulin secretion in a glucose-dependent manner, suppress glucagon, and slow gastric emptying, providing more robust glucose control with significant weight reduction benefits. To implement this recommendation, start by reducing glargine to 4 units for one week, then 2 units for another week before discontinuing completely, while monitoring fasting blood glucose levels daily during the transition. Continue metformin as the foundation therapy since the patient is tolerating it well, and schedule follow-up in 4-6 weeks to assess the effectiveness of the new regimen. It is essential to consider the patient's clinical characteristics, such as the presence of established ASCVD or indicators of high ASCVD risk, other comorbidities, and risk for specific adverse drug effects, as well as safety, tolerability, and cost when selecting the additional medication 1. Ultimately, the goal is to maintain glycemic targets while minimizing side effects and improving the patient's quality of life.
From the FDA Drug Label
2 DOSAGE AND ADMINISTRATION
- 1 Adult Dosage Metformin Hydrochloride Tablets The recommended starting dose of metformin hydrochloride tablets are 500 mg orally twice a day or 850 mg once a day, given with meals. Increase the dose in increments of 500 mg weekly or 850 mg every 2 weeks on the basis of glycemic control and tolerability, up to a maximum dose of 2550 mg per day, given in divided doses.
The patient is already taking metformin 500 mg bid. To discontinue glargine and supplement with oral meds, increasing the dose of metformin could be considered, up to a maximum dose of 2550 mg per day, given in divided doses.
- The dose can be increased in increments of 500 mg weekly or 850 mg every 2 weeks, based on glycemic control and tolerability.
- However, no specific oral medication is recommended in the label to replace glargine. 2
From the Research
Oral Medication Recommendations
To discontinue glargine and supplement with oral medications for a 38-year-old with diabetes type 2 on metformin 500 mg bid and glargine 7 units at night with good glucose control, the following options can be considered:
- Pioglitazone/metformin FDC supplemented with dapagliflozin, as it has been shown to be a safe and effective alternative to basal insulin combined with metformin for rectifying inadequate glucose control 3
- Initial triple combination therapy with metformin, sitagliptin, and empagliflozin, which has been found to lead to achievement of the glycemic target goal, improved metabolic function, and albuminuria without severe hypoglycemia 4
- Adding empagliflozin to pioglitazone or pioglitazone plus metformin, which may offer advantages in terms of significant reductions in glycated hemoglobin levels, weight, and blood pressure, with a low risk of hypoglycemia 5
Comparison of Single-Drug Regimens
A network meta-analysis compared the efficacy of 12 single-drug regimens, including:
- Liraglutide, which was found to be more effective than Glimepiride, Pioglitazone, Sitaglitin, Exenatide, and Glipizide at reducing glycated hemoglobin (HbA1c) levels 6
- Sitagliptin and pioglitazone, which were found to be equally effective in improving HbA1c, but with some differences in terms of lipid indices, weight gain, and SBP 7
Considerations
When selecting an oral medication, it is essential to consider the individual's baseline characteristics, such as lipid profiles, weight, and blood pressure, to make an informed decision. Additionally, the potential risks and benefits of each medication, including the risk of hypoglycemia, weight gain, and genital mycotic infections, should be taken into account.