metformin and insulin in type 2 diabetes

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%.

Reference:

• 1. Wong J, Yue D. Starting insulin treatment in type 2 diabetes. Aust Prescr 2004;27:93-6
• 2. Barnett A et al. Insulin for type 2 diabetes: choosing a second-line insulin regimen. Int J Clin Pract. 2008;62(11):1647-53
• 3. Prescribers' Journal (2000), 40 (1), 38-48.
• 4. Yki-Jarvinen H (2001).Combination therapies with insulin in type 2 diabetes.Diabetes Care;24:758-767.
• 5. personal email communication with Yki-Jarvinen (May 10th 2002)
• 6. British Journal of Diabetes and Vascular Disease (2004); 4(2):71-6.
• 7. Goudswaard AN et al. Insulin monotherapy versus combinations of insulin with oral hypoglycaemic agents in patients with type 2 diabetes mellitus. Cochrane Database Syst Rev 2004;(4):CD003418
• 8. Raskin P et al. Initiating insulin therapy in type 2 diabetes: a comparison of biphasic and basal insulin analogs. Diabetes Care 2005;28:260-5