title: Iatrogenic hypoglycemia in patients with type 2 diabetes: comparison of insulin analog premixes and human insulin premixes.
abstract: Severe iatrogenic--or therapy-induced--hypoglycemia has been associated with mortality rates as high as 10% in patients with type 2 diabetes mellitus (T2DM), and is therefore one of the most significant barriers to glucose management in this patient population. Therapy with modern insulin analogs has been shown to cause significantly less hypoglycemic episodes than human insulins in basal-bolus regimens. This systematic review examines whether a similar benefit has been observed with the insulin analog premixes (aspart 70/30, lispro 75/25, or lispro 50/50) relative to human insulin premix (human 70/30). Consistent with a prior meta-analysis, the results presented here reconfirm that overall hypoglycemia risk is similar after treatment with either an analog premix or a human premix in many populations of patients with T2DM. However, several studies found a benefit for the analog premixes in a subset of patients who were under more challenging glucometabolic conditions, in particular those later in disease progression or those undergoing post-injection exercise. Pharmacokinetic and pharmacodynamic studies indicate that this may occur because a larger proportion of total analog premix activity is absorbed and utilized during the immediate postprandial period, when it is most acutely needed, compared with human premixes. Consequently, with analog premixes, less insulin activity is available during the inter-meal fasting period, when hypoglycemia is most likely to occur. Given the clinical significance of iatrogenic hypoglycemia, these potential hypoglycemic benefits of analog premixes relative to human premixes in some patients with T2DM may need to be factored into the therapeutic decision-making process.
authors.affiliation: New York-Presbyterian/Weill Cornell Medical Center, Manhattan Endocrinology, PLLC, New York, NY 10065, USA. md212@verizon.net
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Martorella
mesh_terms: D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced*; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D061267:Insulin Aspart; D061268:Insulin Lispro
chemical_list: D007328:Insulin; D061268:Insulin Lispro; D061267:Insulin Aspart