How much is too much? Outcomes in patients using high‐dose insulin glargine

Abstract

SummaryBackground and objectivesMany patients with type 2 diabetes mellitus (T2DM) do not achieve glycaemic control targets on basal insulin regimens. This analysis investigated characteristics, clinical outcomes and impact of concomitant oral antidiabetes drugs (OADs) in patients with T2DM treated with high‐dose insulin glargine.MethodsPatient‐level data were pooled from 15 randomised, treat‐to‐target trials in patients with T2DM treated with insulin glargine ± OADs for ≥ 24 weeks. Data were stratified according to whether patients exceeded three insulin dose cut‐off levels (> 0.5, > 0.7 and > 1.0 IU/kg). End‐points included glycated haemoglobin A1c (A1C), fasting plasma glucose, body weight, and overall, nocturnal and severe hypoglycaemia.ResultsData from 2837 insulin‐naïve patients were analysed. Patients with insulin titrated beyond the three doses investigated had significantly higher baseline A1C levels and were younger, with shorter diabetes duration than those at/below cut‐offs (p < 0.05 for all cut‐offs); they also had greater weight gain (p < 0.001 for the > 0.5 and > 0.7 IU/kg cut‐offs) than those who did not exceed the cut‐offs, regardless of concomitant OAD. Patients on concomitant metformin alone had higher insulin doses at Week 24, but achieved greater reductions in A1C, less weight gain and lower hypoglycaemia rates than patients on a concomitant sulfonylurea or metformin plus a sulfonylurea, regardless of whether cut‐offs were exceeded.ConclusionIn patients with T2DM, increasing basal insulin doses above 0.5 IU/kg may not improve glycaemic control; treatment strategies targeting postprandial glucose control should be considered for such patients.

When basal insulin is not enough: A dose–response relationship between insulin glargine 100 units/mL and glycaemic control

“…24 At week 24, participants with insulin titrated beyond the three thresholds had significantly higher mean HbA1c and FPG levels compared with participants at or In addition, participants who exceeded the thresholds also had greater weight gain and a higher likelihood of hypoglycaemia once the threshold was exceeded. 24 Both higher initial doses and increasing dose have been shown to be associated with weight gain. 25,26 In the CREDIT (Cardiovascular Risk Evaluation in people with type 2 Diabetes on Insulin Therapy) trial, 1 year after initiating insulin therapy, mean weight gain was 1.78 kg.…”

“…[24][25][26] In a pooled study of patient-level data from 15 randomized, treat-to-target trials in insulin-naive participants with type 2 diabetes treated with insulin glargine ± oral antidiabetes drugs for ≥24 weeks, data were stratified according to whether participants exceeded daily insulin dose thresholds >0.5, >0.7 and >1.0 IU/kg. [24][25][26] In a pooled study of patient-level data from 15 randomized, treat-to-target trials in insulin-naive participants with type 2 diabetes treated with insulin glargine ± oral antidiabetes drugs for ≥24 weeks, data were stratified according to whether participants exceeded daily insulin dose thresholds >0.5, >0.7 and >1.0 IU/kg.…”

“…[24][25][26] In a pooled study of patient-level data from 15 randomized, treat-to-target trials in insulin-naive participants with type 2 diabetes treated with insulin glargine ± oral antidiabetes drugs for ≥24 weeks, data were stratified according to whether participants exceeded daily insulin dose thresholds >0.5, >0.7 and >1.0 IU/kg. 24 Both higher initial doses and increasing dose have been shown to be associated with weight gain. 24 Both higher initial doses and increasing dose have been shown to be associated with weight gain.…”

“…Previous studies have also shown that insulin doses >0.5 IU/kg/d do not improve glycaemic control and may be associated with both an increased risk of hypoglycaemia and greater weight gain. [24][25][26] In a pooled study of patient-level data from 15 randomized, treat-to-target trials in insulin-naive participants with type 2 diabetes treated with insulin glargine ± oral antidiabetes drugs for ≥24 weeks, data were stratified according to whether participants exceeded daily insulin dose thresholds >0.5, >0.7 and >1.0 IU/kg. 24 At week 24, participants with insulin titrated beyond the three thresholds had significantly higher mean HbA1c and FPG levels compared with participants at or In addition, participants who exceeded the thresholds also had greater weight gain and a higher likelihood of hypoglycaemia once the threshold was exceeded.…”

Response to Umpierrez et al

“…For patients who weigh ≤l00 kg, this translates into >0.6 IU/kg (corresponding nicely with the 46% requiring >0.5 IU/kg in the paper by Umpierrez et al). Indeed, 38% of people with type 2 diabetes in 15 Sanofi phase 3 treat‐to‐target studies using U‐100 glargine insulin required >0.5 IU/kg . At the end of these studies, the mean FPG levels were 6.5 mmol/L (116.6 mg/dL) and 6.7 mmol/L (120.7 mg/dL), respectively, in patients receiving ≤0.5 and >0.5 IU/kg.…”