Different diabetes drugs and how they work

Introduction

Diabetes treatment has changed remarkably over the past 15 years. Until recently the choice was mainly metformin, sulfonylureas and insulin. Today new drug classes are available that, in addition to blood sugar control, also protect the heart and kidneys and help with weight loss.

The choice of drug depends on the patient's profile: age, weight, complications, comorbidities, hypoglycaemia risk and patient preference. That is why a treatment plan is always individual.

1. Metformin

The first-line choice for type 2 diabetes. Reduces glucose production in the liver and improves insulin sensitivity.

• Pros: inexpensive, does not cause hypoglycaemia, protects the heart, weight-neutral or even reduces weight
• Cons: initial gastrointestinal side effects (diarrhoea, nausea), may cause B12 deficiency in long-term use
• Dose: 1500–2000 mg per day, in 1–3 divided doses
• Contraindications: severe kidney failure (eGFR < 30), liver failure

2. SGLT2 inhibitors

Empagliflozin (Jardiance), dapagliflozin (Forxiga), canagliflozin (Invokana). They act in the kidneys, blocking the reabsorption of glucose — glucose is excreted in the urine.

• Pros: lower blood sugar, reduce body weight (2–4 kg) and blood pressure, slow the progression of heart failure and chronic kidney disease. Strong cardio- and renal-protective effect.
• Cons: risk of urinary and genital infections, rare risk of diabetic ketoacidosis
• Suitable for: especially patients with heart failure, nephropathy or excess weight
• Contraindications: type 1 diabetes, severe kidney failure

3. GLP-1 receptor agonists

Liraglutide (Victoza), semaglutide (Ozempic, Rybelsus), dulaglutide (Trulicity), tirzepatide (Mounjaro — a GLP-1 and GIP combination). Injectable (one drug, semaglutide Rybelsus, is also available as a tablet) hormones that mimic the body's own GLP-1 hormone.

• Mechanism: stimulate insulin production when blood sugar is high; reduce glucagon levels; slow gastric emptying; reduce appetite
• Pros: powerful glucose-lowering effect, significant weight loss (5–15%), heart-protective effect
• Cons: expensive, side effects — nausea when starting treatment, occasionally gastrointestinal problems, potential pancreatitis risk
• Suitable for: patients with high HbA1c, overweight patients, patients at high risk of heart attack

4. DPP-4 inhibitors

Sitagliptin (Januvia), linagliptin (Trajenta), vildagliptin (Galvus). They block the DPP-4 enzyme that breaks down the body's own GLP-1 hormone — so they are effectively a weaker version of GLP-1 agonists.

• Pros: tablet form, well tolerated, weight-neutral, do not cause hypoglycaemia
• Cons: weaker effect than GLP-1 agonists, do not reduce weight, do not actively protect the heart
• Suitable for: mild to moderate diabetes, elderly patients

5. Sulfonylureas

Gliclazide (Diaprel MR), glimepiride (Amaryl). The oldest drugs for type 2 diabetes. They stimulate the pancreas to produce more insulin.

• Pros: inexpensive, strong glucose-lowering effect
• Cons: risk of hypoglycaemia, 2–5 kg weight gain, effectiveness wanes over time (beta-cell exhaustion)
• Suitable for: patients with a limited budget when other drugs are not available

6. Thiazolidinediones (TZD)

Pioglitazone (Actos). Improves insulin sensitivity in muscles and the liver.

• Pros: strong improvement of insulin sensitivity, can improve fatty liver
• Cons: weight gain, fluid retention, risk of heart failure, increased osteoporosis risk
• Used less commonly today

7. Insulin

Insulin is the most powerful drug — suitable for all types of diabetes.

Types of insulin:

• Rapid-acting (lispro, aspart, glulisine) — onset 5–15 min, duration 3–5 hours. Injected before meals.
• Long-acting (glargine, detemir, degludec) — onset 1–2 hours, duration 24–42 hours. These are basal insulins, 1–2 injections per day.
• Pre-mixed insulins — a combination of intermediate- and rapid-acting insulin. A simpler regimen but less flexible.

• Pros: always works, powerful, mandatory in type 1 diabetes
• Cons: injectable, risk of hypoglycaemia, weight gain

8. Combination therapy — how it is planned

Most patients with type 2 diabetes need two or more drugs over time. Typical combinations include:

• Metformin + SGLT2 inhibitor (e.g. type 2 diabetes in an overweight patient)
• Metformin + GLP-1 agonist (e.g. type 2 diabetes in a patient at high cardiovascular risk)
• Metformin + DPP-4 inhibitor (e.g. for the elderly when a simple regimen is needed)
• Metformin + SGLT2 inhibitor + basal insulin (when beta-cell function declines)

9. New drugs coming

Diabetes treatment is a rapidly developing field. Coming to market in the near future:

• Triple agonists (GLP-1 + GIP + glucagon — retatrutide) — even greater weight loss than with Mounjaro
• Oral GLP-1 agonists — Rybelsus is already available, more tablets are coming
• Continuous glucose monitoring (CGM) and insulin pumps — significantly easier management of type 1 diabetes

At our clinic

At Tallinn Endocrinology Clinic we select exactly the drugs that suit your profile best — taking into account all side effects, comorbidities and your own preferences. The endocrinologist will assess your status holistically and plan a treatment programme that helps you the most. Book an appointment — together we will find the best solution for you.