In type 2 diabetes, diet, exercise and attaining a healthy weight should be encouraged at every opportunity Metformin is the usual first-line drug management Sulfonylureas are appropriate as second-line drugs for many patients. Other oral drugs are preferable if weight gain or hypoglycaemia are significant problems If a combination of metformin and a sulfonylurea is not suitable, either a dipeptidyl peptidase-4 inhibitor or sodium-glucose co-transporter 2 inhibitor can be prescribed. The patient characteristics and the beneficial and adverse effects of the drug should be considered when selecting second-line therapy Due to their adverse-effect profiles, thiazolidinediones and acarbose should be reserved for patients with contraindications to all other oral drugs, and those who will not tolerate injectable drugs Keywords: incretin mimetics, metformin, oral hypoglycaemic drugs, sodium-glucose co-transporter 2 inhibitors, sulfonylureas, type 2 diabetes Introduction Type 2 diabetes is a common medical condition, with the prevalence increasing to 1 million people in Australia in 2014–15.1 The goals of therapy should be individualised, based on patient characteristics, including age and comorbidities. Diet, exercise and a healthy weight are important components of the management. The range of drugs for type 2 diabetes (see Table) has increased in recent years, delaying the need for insulin therapy, but adding complexity to treatment algorithms. Metformin is first line for drug therapy.2 Sulfonylureas have a major role as second-line drugs, however there are a number of alternative options that should be considered when weight gain and hypoglycaemia are to be avoided. The choice of second-line drug should be individualised, based on the degree and timing of hyperglycaemia, comorbid conditions and the drug’s beneficial and adverse-effect profile. Table Second-line drugs for type 2 diabetes Class Approximate HbA1c reduction* Benefits in addition to glucose-lowering Adverse effects Precautions Sulfonylureas 0.5–1.3% Nil Hypoglycaemia, weight gain Kidney impairment (dose reduction may be required), severe liver disease, elderly Dipeptidyl peptidase-4 inhibitors 0.7–1% Minimal hypoglycaemic risk Pancreatitis Pancreatic disease, kidney impairment (dose reduction may be required) Glucagon-like peptide-1 analogues 0.8–0.9% Weight loss Nausea and vomiting Kidney impairment (contraindicated if CrCl <30 mL/min), pancreatic disease, gallbladder disease, pre-existing gastrointestinal symptoms, family or personal history of thyroid cancer (based on animal models) Sodium-glucose co-transporter 2 inhibitors 0.5–0.7% Lowering of blood pressure, cardioprotection, weight loss Genitourinary infections, euglycaemic ketoacidosis Fasting or peri-operative state, acute intercurrent illness, taking loop diuretics, kidney impairment (contraindicated if CrCl <45 mL/min) Insulin Superior to other diabetes drugs Nil Hypoglycaemia, weight gain Inability to safely administer insulin or monitor glucose Acarbose 0.8% Nil Gastrointestinal symptoms Gastrointestinal disease, kidney impairment (contraindicated if CrCl <25 mL/min), note glucose (not sucrose) must be administered to treat hypoglycaemia Thiazolidinediones 0.7–0.8% Nil Worsening of heart failure, increased fracture risk, macular oedema, cardiac ischaemia, bladder cancer Osteoporosis, macular oedema, heart failure, liver disease Open in a separate window CrCl creatinine clearance * The approximate glycated haemoglobin (HbA1c) reduction is based on studies using the class of drug as adjuvant therapy to metformin.