#35 The long and short of long acting insulin analogues (versus NPH)?
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- A1c: Glargine or determir versus NPH.
- No difference in attaining A1c <7%.
- Mean A1c: Most comparisons not statistically different, and none were clinically significant (e.g. A1c on NPH was 0.28% lower than glargine in patients not on oral medications).
- Hypoglycemia: Glargine (with oral meds).
- Severe hypoglycemia: No statistical difference.
- Overall hypoglycemia (patients with ≥1 episodes):
- Glargine (47.2%) statistically significantly lower than NPH (55.9%), Number Needed to Treat (NNT)=12.
- Nocturnal hypoglycemia (patients with ≥1 episodes):
- Glargine (18.8%) statistically significantly lower than NPH (33.1%), NNT=7
- Hypoglycemia: Detemir (with oral meds).
- Similar to glargine versus NPH (except overall hypoglycemia not different).
- Definitions of hypoglycemia varied considerably.
- Unblinded: Everyone knew who was on which insulin.
- Hypoglycemic symptoms are:
- Non-specific and heterogeneous.3
- Poorly correlated with biochemical hypoglycemia.4,5
- All trials counted unconfirmed (untested) hypoglycemia (including severe).
- Trials were primarily industry-funded with poor quality (e.g. >90% were unclear in explaining how randomizations was assured).
- Cochrane review6 and other reviews7,8,9 of LAIA reported very similar results:
- Cochrane conclusion: LAIA offer “if at all only a minor clinical benefit” and recommend “until long-term efficacy and safety data are available, we suggest a cautious approach to therapy with insulin glargine or detemir.”
- Other issues:
- Weight gain (seven studies): +0.18 kg more with NPH.1
- Cancer risk: Some concern about insulin glargine but the data is observational and not conclusive.10
- Quality of life: Rarely measured but not statistically significant when measured.11,12
- LAIA are not cost-effective.13