insulin in Type 2 diabetes mellitus

Last edited 09/2021 and last reviewed 03/2022

  • the United Kingdom Prospective Diabetes Study Group (UKPDS) has pointed out that majority of type 2 diabetes patients will experience progressive pancreatic beta cell dysfunction even when their diabetes control is excellent (1)
    • so type 2 diabetics may eventually require treatment with insulin when oral hypoglycaemic medication is no longer effective

  • a straight swap to insulin treatment is usual if the maximal therapy with non-insulin treatments have been reached

  • according to estimations in UK general practice, only 50% of patients who require insulin due to failure of oral medication will receive it within 5 years o the average time taken from beginning treatment with the last oral agent to beginning insulin therapy is around 8 years (2)

  • in the case of overweight patients taking metformin, then treatment with metformin may be continued - this is because metformin may attenuate weight gain resulting from the introduction of insulin therapy

  • insulin therapy and a sulphonylurea may decrease the amount of insulin actually required and enhance the use of a single night-time dose but overall the clinical advantages of this combination are small (3)

  • the average weight gain resulting from introduction of insulin therapy is 4 kg - however some patients may have a marked increase in weight after onset of insulin therapy

  • in a comprehensive review of combination therapies with insulin in type 2 diabetes Yki-Jarvinen suggests an algorithm for starting insulin in an insulin naive type 2 diabetic patient who is on maximal oral hypoglycaemic therapy. In this algorithm she suggests stopping sulphonylurea treatment and continuation of metformin at a dose of 2g per day in combination with insulin treatment (4). If the patient is not on a dose of 2g per day when conversion to insulin occurs then the dose of metformin should be increased by 500mg per week until a metformin dose of 2g per day is achieved (5)

  • in consideration of combination of insulin and an oral hypoglycaemic agent in type 2 diabetes:
    • well-designed trials indicate that glargine and NPH bedtime insulin are similarly effective in combination with oral antidiabetic agents, with a superior hypoglycaemic profile for glargine (6)
    • one review concluded that once-daily glargine insulin plus metformin (> 2 g per day), in suitable patients, may be the optimum combination (6)
    • a systematic review analysing the use of bedtime NPH insulin and oral hypoglycaemic agents concluded that:
      • bedtime NPH insulin combined with oral hypoglycaemic agents provides comparable glycaemic control to insulin monotherapy and is associated with less weight gain if metformin is used (7)

  • in consideration as to whether to initiate once or twice daily insulin in type 2 diabetic patients:
    • there is study evidence that (8) in subjects with type 2 diabetes poorly controlled on oral hypoglycaemic agents, initiating insulin therapy with twice-daily biphasic insulin aspart 70/30 (prebreakfast and presupper) BIAsp 70/30 was more effective in achieving HbA(1c) targets than once-daily glargine, especially in subjects with HbA(1c) >8.5%.