Newer Oral Antidiabetic Agents

Metformin remains first-line after lifestyle measures in older adults; it lowers glucose without hypoglycaemia, causes modest weight loss, reduces microvascular complications, and reduced cardiovascular events and mortality in obese patients in UKPDS.

Long-term metformin causes vitamin B12 deficiency; periodic measurement is advised. It must be avoided in severe renal impairment and withheld in dehydration, sepsis and before contrast or surgery.

Newer agents were developed because sulphonylureas cause hypoglycaemia and weight gain and thiazolidinediones cause fluid retention, heart failure and fractures — both particularly hazardous in the elderly.

Sitagliptin, vildagliptin, linagliptin, saxagliptin, alogliptin, teneligliptin inhibit degradation of GLP-1 and GIP, giving a near-physiological, glucose-dependent incretin effect.

HbA1c reduction 0.5–1.0%; weight neutral, no intrinsic hypoglycaemia, minimal adverse effects — making them among the safest agents in frail older adults.

Linagliptin needs no dose adjustment in renal failure (CARMELINA showed cardiovascular and renal safety in high-risk patients); others require dose reduction.

As a class they are cardiovascular-neutral; saxagliptin increased heart-failure hospitalisation (SAVOR-TIMI 53) and is best avoided in cardiac patients.

Empagliflozin, dapagliflozin, canagliflozin, ertugliflozin block proximal tubular glucose reabsorption, giving insulin-independent glycosuria.

HbA1c reduction 0.5–1.0%, with weight loss of 2–3 kg, blood pressure reduction, and no hypoglycaemia when used alone.

Empagliflozin and canagliflozin reduce MACE; empagliflozin reduces cardiovascular death, heart-failure hospitalisation and worsening nephropathy — benefits now extended to patients without diabetes.

Cautions in the elderly: volume depletion, postural hypotension and falls, genital mycotic infection, urinary infection, euglycaemic ketoacidosis, weight loss aggravating sarcopenia, and (with canagliflozin) amputation risk.

Oral semaglutide (Rybelsus) is the first orally available GLP-1 receptor agonist; it must be taken fasting with ≤120 mL water and 30 minutes before food.

GLP-1 receptor agonists lower HbA1c by 1.0–2.0%, cause weight loss of 1.6–3 kg or more, and liraglutide, semaglutide and dulaglutide reduce cardiovascular events in high-risk patients.

In older adults, nausea, vomiting, anorexia, weight loss and sarcopenia limit their use; a 43% discontinuation rate was seen with exenatide in participants aged ≥65.

Choose by renal and hepatic function, frailty, hypoglycaemia risk, cardiac and renal comorbidity, cost and swallowing ability — not by HbA1c alone.

Consider a glinide (repaglinide) if eating is irregular, avoid SGLT2 inhibitors where weight loss, dehydration or foot disease predominate, and use gliclazide if a sulphonylurea is unavoidable.

De-intensification (deprescribing) is an active clinical duty in those who are frail, underweight, cognitively impaired or renally impaired — simplification or withdrawal is usually feasible without loss of control.

In India, cost, availability of generic teneligliptin, vildagliptin and dapagliflozin, and coverage under AB-PMJAY strongly influence choice; screen for tuberculosis and genital/urinary infection before starting SGLT2 inhibitors.