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#20 Strategies for initiating insulin in Type 2 Diabetics

What is the optimal regimen for initiating insulin in type 2 diabetes

In type 2 diabetes poorly controlled with oral agents, initiating basal insulin results in similar HbA1c reductions compared to prandial or biphasic insulin and may cause less weight gain and hypoglycemia. Family practitioners who start insulin are as effective as specialists.

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Five reasonably-sized randomized controlled trials compare regimens for initiating insulin in type 2 diabetes with poor glucose control.  
  • 4T study1: Followed 708 patients for 3 years comparing long-acting basal insulin once daily, biphasic premixed insulin twice daily or prandial insulin with meals.1  
    • HbA1c levels were not significantly different between the three groups,  
      • Significantly more patients in the basal and prandial groups attained HbA1c ≤7.0% (63% and 67% versus 49% biphasic).   
    • Basal insulin had statistically significant: 
      • Less weight gain (3.6kg) than prandial (6.4kg) or biphasic insulin (5.7kg),   
      • Fewer confirmed symptomatic hypoglycemic events/person/yr (1.7 basal versus 3.0 biphasic, versus 5.7 prandial), 
      • More patients requiring a second type of insulin (82% basal, 74% prandial and 68% biphasic), 
      • Higher total dose of insulin (by weight).   
  • The four remaining studies (APOLLO2, INITIATE3 JDDM 114, and Riddle5) followed 160 to 588 patients for 6-14 months and compared basal to prandial,2 basal to biphasic,3 biphasic to prandial,4 and basal(+/-prandial) to biphasic5 insulin.   
    • HbA1c was generally similar except biphasic improved HbA1c more and got more people to a HbA1c ≤7.0% than basal in one study,3 but less than basal+prandial in another.5 
    • Basal insulin had significantly less hypoglycemia (than prandial2 or biphasic3) and weight gain (than biphasic3), and basal(+/-prandial) had less hypoglycemia and weight gain than biphasic.5 
  • Meta-analysefound similar.6,7 
  • 4T studyis given priority because it is the largest, longest and compares the three options.  Fortunately, the remaining studies2-5 generally support those findings.    
  • INSIGHT8 found initiating basal insulin in poorly controlled type 2 diabetes resulted in significantly lower HbA1C than continued oral hypoglycemic agents 
    • Mean HbA1c and hypoglycemic rates were not different between patients of family practitioners or diabetes experts.9 
  • There is no evidence that insulin is superior to oral agents in reducing clinical outcomes in patients with type 2 diabetes.10 
  • Specialists are five times more likely to initiate insulin than family practitioners.11  
updated dec 6 2017 by ricky

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  • Christina Korownyk MD CCFP
  • G. Michael Allan MD CCFP
  • Noah Ivers MD CCFP

1. Holman RR, Farmer AJ, Davies MJ, et al. N Engl J Med. 2009 Oct 29;361(18):1736-47.

2. Bretzel RG, Nuber U, Landgraf W, et al. Lancet. 2008 Mar 29; 371(9618):1073-84.

3. Raskin P, Allen E, Hollander P, et al. Diabetes Care. 2005 Feb; 28(2):260-5.

4. Hirao K, Arai K, Yamauchi M, et al. Diabetes Res Clin Pract. 2008 Jan; 79(1):171-6.

5. Riddle MC, Rosenstock J, Vlajnic A, Gao L. Diabetes Obes Metab. 2014;16:396-402.

6. Pontrioli AE, Miele L, Morabito A. Diabetes Obes Metab. 2012 May; 14(5):433-46.

7. Wang C, Mamza J, Idris I. Diabet Med. 2015;32:585-594.

8. Gerstein HC, Yale JF, Harris SB, et al. Diabet Med. 2006 Jul; 23(7):736-42.

9. Harris S, Yale JF, Dempsey E, et al. Can Fam Physician. 2008 Apr; 54(4):550-8.

10. Palmer SC, Mavridis D, Nicolucci A, et al. JAMA. 2016;316(3):313-324.

11. Shah BR, Hux JE, Laupacis A, et al. Diabetes Care. 2005 Mar; 28(3):600-6.

Authors do not have any conflicts of interest to declare.