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The past few years have brought on a new array of oral hypoglycaemic agents.

hypoglycaemic agents 

For patients whose glycaemic control is suboptimal despite being on Metformin and Sulphonylureas, the following oral hypoglycaemic drugs may be considered as part of combination therapy.

Alpha-Glucosida SE Inhibitors

Acarbose works by inhibiting intestinal α-glucosidase which slows intestinal carbohydrate digestion and absorption. Common gastrointestinal side effects such as flatulence and diarrhoea are observed. However, its efficacy of reduction in HbA1c is modest.

Dipeptidyl Peptida SE 4 (DPP-4) Inhibitors

They work by inhibiting DPP-4 activity, thus increasing post-prandial active incretin concentrations. Raised incretin levels in turn inhibits glucagon release, leading to increased insulin secretion, delayed gastric emptying and lowering of blood glucose.

Potential side effects include joint pain and gastrointestinal symptoms such as nausea and diarrhoea. It should be avoided in patients at risk of pancreatitis. It also has a lower risk of hypoglycaemia and may be viable alternative to Sulphonylureas in the elderly or patients prone to hypoglycaemia.

Sodium-Glucose Cotransporter

2 (SG LT2) inhibitors These class of agents work by inhibiting SGLT2 in the proximal nephron thus decreasing glucose reabsorption and leading to an increase in urinary glucose excretion. Other potential advantages include modest weight loss and blood pressure lowering.

Genital fungal infections and urinary tract infections are potential side effects. In view of its diuretic effect, it should be used with caution in the elderly and patients with postural hypotension.

Glucagon-Like Peptide 1 (GLP-1) Receptor Agonist

Similar to DPP-4 inhibitors, it targets the incretin system. It increases insulin release while decreasing glucagon release and delays gastric emptying. GLP-1 agonists are administered via subcutaneous injection. It also has additional benefits of weight loss and lower risk of hypoglycaemia.

Gastrointestinal side effects such as nausea and diarrhoea may occur although they are usually transient.

Caution should be practised in patients with a history of pancreatitis. A new agent, which is a combination of longacting basal insulin and GLP-1 agonist, has recently been approved in Europe after showing promising clinical results.

Metformin remains the optimal drug for monotherapy. In instances where Metformin is not tolerated or contraindicated, Sulphonylureas or one of the above agents may be used.

However, if renal impairment is the reason it is avoided, the choices becomes more limited. In such cases, short-acting Sulphonylureas, DPP-4 inhibitors (renal adjusted dose) and/or insulin therapy, may be considered.

As β-cell function deteriorates with increasing duration of diabetes, patients may still fail to reach glycaemic targets despite combination therapy with two or three oral agents. In this group of patients, insulin therapy is still required (either alone or in combination with oral agents) to optimise glucose control. Also, in patients with a high HbA1c and glucotoxicity at initial presentation, insulin should be instituted.

The treatment of diabetes mellitus is highly individualised with many factors to be taken into consideration such as age, risk of hypoglycaemia, comorbidities and contraindications. As more and more drugs are introduced to the market, it is also imperative that prescribers should remain aware of the cost-benefit considerations for each patient.

Dr Shariffah Nadia Aljunied

Dr Shariffah Nadia Aljunied
Resident Physician
Department of Endocrinology
Tan Tock Seng Hospital

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