From the Guidelines

The first-line treatment for type 2 diabetes is metformin, as recommended by the most recent guidelines 1.

Metformin should be initiated at a dose of 500 mg once or twice daily with food and titrated gradually to the maximum effective dose of 2 g/d, as it is effective, safe, and inexpensive, and may reduce the risk for cardiovascular events and death 1.
A patient-centered approach should be used to guide the choice of pharmacologic agents, considering factors such as efficacy, hypoglycemia risk, effect on weight, side effects, cost, and patient preferences 1.
Lifestyle modifications, including regular physical activity, dietary changes, and weight loss, are essential components of first-line treatment, and should be implemented alongside medication.
If metformin is contraindicated or poorly tolerated, alternative first-line options include SGLT-2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, or sulfonylureas, selected based on patient-specific factors like cardiovascular risk, weight concerns, and hypoglycemia risk 1.

Metformin may be safely used in patients with an estimated glomerular filtration rate as low as 30 mL/min/1.73 m2, and periodic testing of vitamin B12 levels should be considered in metformin users, especially those with anemia or peripheral neuropathy 1.
The choice of agent should be based on evidence that moves beyond HbA1c, and should consider the strong evidence for agents from the GLP1-RA and SGLT2i class, which have been shown to have cardiovascular benefits 1.

From the Research

The first-line treatment for type 2 diabetes is a topic of ongoing debate, with various studies suggesting different approaches.

Metformin has been considered the first-line oral therapy for type 2 diabetes for the past two decades, due to its glycaemic benefit and relatively safe adverse effect profile 2, 3, 4.
However, recent guidelines suggest that other agents, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP1) receptor agonists, may be considered as first-line treatment in patients with higher cardiovascular risk 3, 5, 4.
Insulin therapy is also an option for type 2 diabetes, particularly when oral glucose-lowering drugs are not sufficient to achieve good glucose control 6.

The following treatment options are available for type 2 diabetes:

Metformin: increases the sensitivity of the liver and peripheral tissues to insulin, and is considered the first-line oral therapy for type 2 diabetes 2, 3, 4.
SGLT2 inhibitors: recommended for people with atherosclerotic cardiovascular disease, heart failure, or kidney disease 5.
GLP1 receptor agonists: recommended for people with atherosclerotic cardiovascular disease 5.
Insulin therapy: may be necessary for patients with type 2 diabetes who are not responding to oral glucose-lowering drugs 6.
Alpha-glucosidase inhibitors: improve the time relationship between plasma insulin and glucose increases after a meal, and may be used in combination with insulin secretagogues 2.

When selecting a treatment for type 2 diabetes, the following factors should be considered:

Cardiovascular risk: patients with higher cardiovascular risk may benefit from SGLT2 inhibitors or GLP1 receptor agonists 3, 5.
Kidney disease: patients with kidney disease may benefit from SGLT2 inhibitors 5.
Insulin resistance: patients with insulin resistance may benefit from metformin or thiazolidinediones 2.
Hypoglycemia risk: patients at risk of hypoglycemia may benefit from agents that do not increase the risk of hypoglycemia, such as metformin or SGLT2 inhibitors 2, 5.