Relative Contribution of Fasting and Postprandial Blood Glucose in Overall Glycemic Control: Post Hoc Analysis of a Phase IV Randomized Trial

Abstract

IntroductionFew prospective clinical trials have investigated the role of fasting blood glucose (FBG) and/or postprandial glucose (PPG) in assessing overall glycemic control by using different insulin regimens. In the present post hoc analysis, we assessed the contribution of FBG and/or PPG in overall glycemic control in Chinese patients under insulin treatment.MethodsCLASSIFY is a phase IV, randomized, open-label, 26-week, parallel-arm, treat-to-target, multinational, controlled study in patients with type 2 diabetes mellitus to compare the efficacy and safety of insulin lispro mix 25 (LM25) and insulin lispro mix 50 (LM50) as starter insulins. Insulin was titrated with an aim to target pre-meal blood glucose (BG) levels at > 3.9 and ≤ 6.1 mmol/L before breakfast and dinner. The primary outcome assessed was the change in HbA1c from baseline.ResultsChinese patients contributed 38.7% (N = 156) of the total population. The majority of patients were male (52.6%). The mean (SD) body mass index was 24.54 (3.04) kg/m2 and mean (SD) HbA1c was 8.54 (1.10) % at baseline. At week 26, LM50 showed a significantly greater reduction from baseline in HbA1c (− 2.03% vs − 1.55%, P < 0.001), average daily BG (− 3.21 vs − 2.34 mmol/L, P < 0.001), average post-meal BG (− 3.58 vs − 2.39 mmol/L, P < 0.001), and average prandial BG excursion (− 1.01 vs − 0.22 mmol/L, P = 0.006) than the LM25 group. The reductions in average pre-meal BG (− 2.59 vs − 2.28 mmol/L, P = 0.137) were not significantly different between the groups. The proportion of patients achieving HbA1c targets (< 7% or ≤ 6.5%) without nocturnal hypoglycemia or weight gain was greater (P < 0.05) with LM50 compared with LM25.ConclusionLM50 achieved better overall glycemic control than LM25 as a starter insulin in Chinese patients, which may be due to greater improvement in PPG levels.Trial RegistrationClinicaltrials.gov identification number: NCT01773473.FundingEli Lilly and Company, Shanghai, China.

A new approach for investigating the relative contribution of basal glucose and postprandial glucose to HbA1C

“…Recent studies of diabetes patients being administered insulin [20][21][22] and Glucagon like peptide-1 receptor agonists (GLP-1 RAs) 23 are a good complement to our research. These studies also revealed that BG plays a major role in the subgroup of patients with HbA1c levels > 8.5%, and the relative contribution of PPG decreased with increasing HbA1c (from 65.5% to 39.2%).…”

“…BG predominated when HbA1c was ≥9and ≥ 10% in oral antidiabetic drug- and insulin-treated patients. Li et al 20 , 22 (2018) 81 (a) T2DM treated with insulin (b) LM25 and LM50 (c)Chinese, China ≥6.1 (a) 4-point blood glucose profile at least one day (b) high-carbohydrate test meals on day 1 and high-fat test meals on day 2 and their habitual diets on day 3 7.8 ± 1.4 PPG played a major role of patients with HbA1c < 8.5%. PPG’s contribution rate decreased with increasing HbA1c (from 65.5% to 39.2%).…”

“…However, the A1 C -derived average glucose study 8 showed that BG was not a clear indicator of general glycaemia. Table 1 summarizes 17 relevant studies 6,7,[9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] published up to Jan 1, 2021. It shows the complex results on the relative contribution of PPG to HbA1c in diverse subjects, treatment regimens, and baseline criterias.…”

“…0%),22.8% (HbA1c > 9.0%). Overestimated for 10-20% choosing 6.1 mmol/L as baseline compared with NGT curve.…”

Contribution of BHG and PPHG to Overall Hyperglycemia in T2DM Patients Treated with LM25 and LM50: Post Hoc Analysis of a Randomized Crossover Trial

“…At present, there are several clinical trials directly comparing the effects of LM25 and LM50 on fasting hyperglycemia, postprandial hyperglycemia, and HbA 1c [ 27 – 31 ]. Our study and the above studies all showed that LM50 was more effective than LM25 in reducing postprandial blood glucose after the morning and evening meals, reducing prandial blood glucose excursion or stabilizing blood glucose excursion during the daytime [ 24 ].…”