What is the first-line therapy for diabetes?

From the Guidelines

The first-line therapy for type 2 diabetes is metformin, typically started at 500 mg once or twice daily with meals, gradually increasing to a target dose of 1000-2000 mg daily (divided into two doses) as tolerated, as recommended by the most recent guidelines 1. This approach is supported by the American College of Physicians and is based on the effectiveness of metformin in lowering blood glucose with minimal hypoglycemia risk, its weight-neutral or modest weight loss effects, cardiovascular benefits, and low cost. Key points to consider when initiating metformin therapy include:

• Starting with a low dose to minimize gastrointestinal side effects such as diarrhea and nausea
• Gradually increasing the dose as tolerated to achieve the target dose
• Implementing lifestyle modifications alongside medication, including regular physical activity, dietary changes, and weight loss if overweight
• Monitoring for potential side effects and adjusting the treatment plan as needed
• Considering alternative or additional therapies if metformin is contraindicated or not effective, with a patient-centered approach taking into account individual preferences, comorbidities, and management needs 1. It's also important to note that for type 1 diabetes, insulin therapy is the first-line treatment from diagnosis, as these patients cannot produce insulin and require lifelong replacement. Overall, the goal of first-line therapy for type 2 diabetes is to achieve glycemic control while minimizing risks and improving quality of life, with metformin being the preferred initial treatment option due to its efficacy, safety, and cost-effectiveness 1.

From the FDA Drug Label

Metformin hydrochloride tablets

What is type 2 diabetes Type 2 diabetes is a condition in which your body does not make enough insulin, and the insulin that your body produces does not work as well as it should.

The main goal of treating diabetes is to lower your blood sugar to a normal level.

High blood sugar can be lowered by diet and exercise, and by certain medicines when necessary.

The first-line therapy for diabetes is metformin, as it is the medication described in the provided drug label.

• Key points:
  • Metformin is used to treat type 2 diabetes.
  • The main goal of treating diabetes is to lower blood sugar to a normal level.
  • High blood sugar can be lowered by diet, exercise, and certain medicines when necessary. 2

From the Research

First-Line Therapy for Diabetes

• Metformin is considered the first-line pharmacological treatment for patients with type 2 diabetes mellitus due to its favorable overall profile, including its glucose-lowering ability, weight-neutral effects, and low risk of hypoglycemia 3, 4.
• The UK Prospective Diabetes Study (UKPDS) demonstrated a substantial beneficial effect of metformin therapy on cardiovascular disease (CVD) outcomes, with a 36% relative risk reduction in all cause mortality and a 39% relative risk reduction in myocardial infarction 4.
• Metformin is recommended as the first-line foundation therapy, in addition to lifestyle interventions, by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) consensus guidelines on the management of hyperglycaemia in type 2 diabetes 4.
• When metformin is contraindicated or not tolerated, other classes of agents can be used as initial monotherapy, including dipeptidyl peptidase-4 (DPP-4) inhibitors 5, 6.

Combination Therapy

• The combination therapy of DPP-4 inhibitors and metformin provides excellent efficacy and safety in patients with type 2 diabetes, and is recommended as an add-on, initial combination, or fixed-dose combination (FDC) therapy 7.
• DPP-4 inhibitors can be used as monotherapy when metformin is contraindicated or not tolerated, and can also be used in triple therapies with metformin and SGLT-2 inhibitors or with metformin and insulin 6.

Clinical Use of DPP-4 Inhibitors

• DPP-4 inhibitors stimulate insulin secretion and inhibit glucagon secretion by elevating endogenous GLP-1 concentrations without an intrinsic hypoglycaemia risk, and have a favorable safety profile 6.
• Guidelines suggest the additional use of DPP-4 inhibitors after metformin failure in patients that do not require antidiabetic therapy with proven cardiovascular benefit 6.