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Hypoglycaemic agents and type 2 diabetes: metformin should be the first-line drug treatment

Metformin is the only drug that appears to prevent some complications of diabetes and reduce the mortality of type 2 diabetes patients.

Type 2 diabetes is a frequent disease primarily affecting adults over the age of 40. The aim of treatment is to avoid or delay the occurrence of severe, sometimes fatal complications. It relies firstly on diet and exercise, and if this is not sufficient, medication. No studies have yet been published that provide evidence that any drug other than metformin – for which the evidence is shaky – reduces overall mortality or diabetes-related mortality. Apart from metformin, glibenclamide is the only hypoglycaemic drug which, according to the comparative data, seems to offer some efficacy in preventing the clinical complications of type 2 diabetes, but the level of evidence is very low. Insulins are effective in reducing blood glucose levels, depending on the dose. They expose patients to hypoglycaemia, weight gain, and possibly a risk of cancer. Most more recent drugs have an unfavourable harm-benefit balance.

When metformin is not sufficient to reduce the HbA1c to around 7%, it is sometimes preferable to abandon a strict control of blood glucose levels, especially when life expectancy is short. Other options for consideration on a case-by-case basis are:

  • blood glucose control with sulphonylurea monotherapy:
    • either glibenclamide, if one is to go by the rather flimsy evidence of the UK Prospective Diabetes Study (UKPDS),
    • or else glimepiride, gliclazide or glipizide (not the sustained-release form), whose harm-benefit balances are no better than that of glibenclamide;
  • insulin alone or in combination with metformin;
  • or even the addition of exenatide or liraglutide to metformin, although the long-term harm-benefit balance is uncertain.

©Prescrire 1 May 2015

"Glucose-lowering treatment of type 2 diabetes. Part II - Glucose-lowering drugs after metformin: a choice based largely on adverse effects" Prescrire Int 2015; 24 (160): 130-135. (Pdf, subscribers only).

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See also:

Hypoglycaemic therapy
in type 2 diabetes. Part I -
Metformin is the only
glucose-lowering drug known
to prevent complications
of diabetes
Prescrire Int 2015:
24 (159): 105.
Pdf, subscribers only

Glucose-lowering drugs
in type-2 diabetes
(April 2015)

Type 2 diabetes and metformin.
First choice for monotherapy:
weak evidence of efficacy
but well-known and
acceptable adverse effects
Prescrire Int 2014;
23 (154) : 269-27.
Pdf, subscribers only

Dietary measures for type 2
diabetes. Weight loss and
a Mediterranean-type diet,
with no foods off-limits
Prescrire Int 2009;
18 (103): 224.
Pdf, subscribers only

Numerous other texts available
via the Search function,
using the keywords
"diabetes mellitus"