Metformin
Reduces liver glucose output. Low cost, extensive experience, little hypoglycaemia alone.
- Watch
- GI effects, B12, kidney function; hold in selected acute illness and procedures.
Beyond glucose alone
The right diabetes drug may protect more than blood sugar.
Compare established medicines, SGLT2 inhibitors, GLP-1 and dual GIP/GLP-1 drugs, insulin and the next wave in development.
Explore the treatment map
HbA1c
Glucose control
Weight
Loss, neutrality or gain
Heart
Events and heart failure
Kidney
Slower progression
Burden
Cost, dosing and side effects
Why combinations happen
Type 2 diabetes is several problems at once
Insulin resistance, declining beta-cell function, liver glucose output, kidney glucose handling, appetite and cardiovascular disease do not respond identically to one medicine. Combining classes can improve control with complementary effects.
More tablets are not automatically better. Treatment should be reviewed for benefit, hypoglycaemia, interactions, cost, kidney function and complexity. Type 1 diabetes still requires insulin; no tablet or injection discussed here replaces it.
The medicine map
Established, newer and emerging
Status and access vary by country and indication.
Sulfonylureas
Gliclazide, glimepiride and relatives stimulate insulin release. Effective and inexpensive.
- Trade-off
- Hypoglycaemia and weight gain; benefit is mainly glucose lowering.
Insulin
Life-saving in type 1 and often required in type 2, pregnancy, severe illness or marked hyperglycaemia.
- Watch
- Hypoglycaemia, dosing errors, weight and access. Never stop basal insulin in type 1.
DPP-4 inhibitors
Sitagliptin, linagliptin and others prolong the body's own incretin signals, modestly lowering glucose with low hypo risk and neutral weight.
- Place
- Simple, well-tolerated oral option; do not combine with GLP-1 therapy because added benefit is minimal.
SGLT2 inhibitors
Empagliflozin, dapagliflozin and others increase urinary glucose loss and reduce heart-failure and kidney events in suitable patients.
- Watch
- Genital infections, dehydration and rare euglycaemic ketoacidosis.
GLP-1 receptor agonists
Semaglutide, dulaglutide and liraglutide improve glucose, reduce appetite and weight; selected agents improve cardiovascular outcomes.
- Watch
- GI effects, gallbladder disease, dehydration and delayed gastric emptying.
Dual GIP/GLP-1 agonists
Tirzepatide is the first widely used member, producing powerful HbA1c and weight reductions. More dual and triple agonists are in development.
- Reality
- Still requires long-term adherence; GI effects, availability and cost commonly limit use.
Thiazolidinediones (TZDs)
Pioglitazone improves insulin sensitivity and can be durable and inexpensive; rosiglitazone use is more restricted or uncommon in many places.
- Watch
- Fluid retention, weight gain and fractures; avoid in symptomatic heart failure.
Meglitinides
Repaglinide and nateglinide trigger short insulin release around meals. Flexible dosing may help irregular meal patterns.
- Trade-off
- Hypoglycaemia and weight gain remain possible; frequent dosing and limited outcome advantages reduce use.
Alpha-glucosidase inhibitors
Acarbose and related drugs slow carbohydrate digestion and blunt after-meal glucose rises without causing hypos alone.
- Trade-off
- Gas, bloating and diarrhoea commonly limit use; treat a hypo with glucose, not ordinary table sugar.
Amylin analogues
Pramlintide supplements the amylin signal missing with insulin deficiency, slowing stomach emptying and reducing post-meal glucagon and appetite.
- Watch
- Extra injections, nausea and severe hypoglycaemia unless mealtime insulin is carefully reduced.
Triple agonists and beyond
GLP-1/GIP/glucagon agonists, amylin combinations, once-monthly injections and beta-cell strategies remain in trials.
- Rule
- A trial result is not approval, availability or proof of long-term safety.
The GLP-1 market
Injection, peptide tablet or small-molecule pill?
Oral convenience does not make products interchangeable.
Semaglutide, dulaglutide; dual tirzepatide
High efficacy and simple weekly dosing, but needle acceptance, refrigeration rules, shortages and price matter.
Oral semaglutide
Approved for type 2 diabetes. Absorption is low and variable, so it must be taken exactly as directed on an empty stomach with limited water and a wait before food or other tablets.
Orforglipron
FDA-approved in 2026 for obesity under the US brand Foundayo. Diabetes evidence is substantial, but approval, label and availability must be checked country by country.
Does oral work as well?
It depends on the molecule, dose, endpoint and adherence. Oral semaglutide can produce strong HbA1c lowering but administration is demanding. Newer non-peptide pills avoid injection and fasting rules, yet head-to-head outcomes, tolerability, price and long-term cardiovascular evidence determine whether convenience becomes equivalent value.
Interactive comparison
What outcome matters most?
This teaches the discussion; it does not select treatment.
Choose a priority to see the classes commonly discussed.
Sick days, fasting and surgery
Some medicines become risky when eating stops
Every person having surgery, endoscopy, sedation or severe illness should give the treating team a complete diabetes-medication list.
Ketoacidosis with near-normal glucose
Guidelines advise stopping most SGLT2 inhibitors three days before elective surgery and ertugliflozin four days before. Acute illness, fasting, low-carbohydrate intake and insulin reduction increase risk. Restart only when clinically well and eating, under advice.
Delayed stomach emptying and aspiration
Nausea, vomiting and retained stomach contents can complicate anaesthesia. Current guidance favours individual assessment based on symptoms, dose escalation, drug, procedure and urgency; some higher-risk patients use a 24-hour liquid plan or full-stomach precautions.
Acute illness and lactic acidosis risk
Usually held on the day of surgery and during significant dehydration, hypoxia or acute kidney injury. Contrast and restart decisions depend on kidney function and local protocol.
Hypoglycaemia
Fasting requires an explicit dose plan. Basal insulin is usually adjusted, not simply stopped; sulfonylureas are generally withheld for procedures.
Urgent help: vomiting, abdominal pain, rapid breathing, severe weakness, confusion, ketones, persistent hypoglycaemia or inability to keep fluids down needs prompt clinical advice. DKA can occur without very high glucose on an SGLT2 inhibitor.
Price is not what everyone pays
Cost, subsidy and cost-effectiveness
Eligibility rules frequently differ for diabetes and obesity even when the same molecule is used.
PBS-listed diabetes medicines can reduce patient cost when restriction criteria are met. In 2026 an Ozempic pen showed a published PBS price around A$135 before subsidy and a listed general patient contribution of A$25; obesity-only use may not qualify.
Check PBSList prices, insurance formularies, Medicare rules and manufacturer programmes create very different net prices. Uninsured monthly costs for branded incretins can be hundreds to over US$1,000.
Medicare coverageNHS access follows NICE recommendations and local pathways; eligible prescriptions use normal NHS charging rules in England and are free in some UK nations.
NICE diabetes guidanceProvincial formularies, special-authority rules and private insurance determine coverage; national approval does not guarantee public reimbursement.
Canada's Drug Agency
QALYs and value
Cost-effectiveness changes with baseline cardiovascular and kidney risk, drug price, duration, weight effects and avoided dialysis or hospitalisation. SGLT2 inhibitors are often most valuable in heart failure or chronic kidney disease; high-priced GLP-1 therapies may be cost-effective in selected high-risk groups but not at every price. Ask for absolute benefit, not only relative risk.
Authoritative starting points
Verify the label and the guideline
A-Z medicine appendix
Generic names, brands and safety information
Start with the patient guide; use the official label for complete contraindications, interactions, pregnancy, children, older age, organ impairment and overdose information.
Use the exact product label. Generic name, strength, formulation and brand all matter.