What are the starting drugs for type 2 diabetes mellitus (Dm)?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: June 5, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

Metformin is the preferred initial pharmacologic agent for the treatment of type 2 diabetes mellitus. The typical starting dose is 500 mg once or twice daily with meals, gradually increasing to a target dose of 1000-2000 mg daily in divided doses to minimize gastrointestinal side effects 1. This recommendation is based on the efficacy, safety, tolerability, low cost, and extensive clinical experience with metformin, as well as its ability to reduce the risk of cardiovascular events and death 1.

Key Considerations

  • Metformin should be continued as long as it is tolerated and not contraindicated, with other agents added to metformin as needed to achieve glycemic targets 1.
  • Long-term use of metformin may be associated with biochemical vitamin B12 deficiency, and periodic measurement of vitamin B12 levels should be considered in metformin-treated patients, especially in those with anemia or peripheral neuropathy 1.
  • A patient-centered approach should be used to guide the choice of pharmacologic agents, considering comorbidities, hypoglycemia risk, impact on weight, cost, risk for side effects, and patient preferences 1.

Alternative Therapies

If metformin alone is insufficient to achieve glycemic targets or is contraindicated, alternative starting medications may include:

  • Sulfonylureas (like glipizide or glimepiride)
  • DPP-4 inhibitors (like sitagliptin)
  • SGLT-2 inhibitors (like empagliflozin or dapagliflozin)
  • GLP-1 receptor agonists (like semaglutide)
  • Thiazolidinediones (like pioglitazone)

These alternatives should be chosen based on individual patient characteristics, comorbidities, and preferences, with consideration of their potential benefits and risks 1.

From the FDA Drug Label

For insulin-naïve patients with type 2 diabetes who are inadequately controlled on oral antidiabetic drugs, LEVEMIR should be started at a dose of 0.1 to 0. 2 U/kg once-daily in the evening or 10 units once- or twice-daily, and the dose adjusted to achieve glycemic targets. The starting drug for type 2 diabetes mellitus (Dm) mentioned is LEVEMIR (insulin), which can be started at a dose of 0.1 to 0.2 U/kg once-daily in the evening or 10 units once- or twice-daily for insulin-naïve patients who are inadequately controlled on oral antidiabetic drugs 2.

  • The dose should be adjusted to achieve glycemic targets.
  • Close glucose monitoring is recommended during the transition and in the initial weeks thereafter.

From the Research

Starting Drugs for Type 2 Diabetes Mellitus (Dm)

  • Metformin is commonly used as the first-line agent in the management of type 2 diabetes mellitus (Dm) due to its efficacy, low cost, weight neutrality, and good safety profile 3, 4.
  • However, newer agents such as sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists are favored as the first-line therapy in individuals with type 2 diabetes who would benefit from cardio-renal protection 3, 5.
  • Pioglitazone, a thiazolidinedione, can be administered in combination with metformin, sulfonylureas, or insulin to improve glycemic control with an extremely low incidence of hypoglycemia 6.
  • The choice of starting drug for type 2 diabetes mellitus (Dm) depends on various factors, including the patient's risk profile, glycemic control, and the presence of comorbidities such as heart failure or renal disease 7.
  • Recent guidelines suggest that metformin can be used as the first-line agent, but the initiation of newer glycemic-lowering medications with cardiovascular benefits should be considered in high-risk patients regardless of glycemic control or target HbA1c 7.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.