Predictive and Explanatory Factors of Change in HbA1c in a 24-Week Observational Study of 66,726 People With Type 2 Diabetes Starting Insulin Analogs

Abstract

OBJECTIVEIndividualization of therapy choices requires the prediction of likely response. Predictor and explanatory factors of change in HbA 1c were studied using data from a large observational study of starting insulin analog therapy (the A 1 chieve study). RESEARCH DESIGN AND METHODSUnivariate analyses were performed for insulin-naive people and prior insulin users in the A 1 chieve study. Statistically significant factors were carried forward to baseline factor-only multivariate analyses ("predictor" analysis), and separately using all significant factors ("explanatory" analysis). Power was considered in terms of the variance explained. RESULTSGeographical region, baseline HbA 1c level, lipid levels, and baseline insulin dose were the most powerful predictors of HbA 1c change (mean change 22.1% [223 mmol/mol]) observed in the univariate analysis (r 2 > 0.010, P < 0.001). However, although the predictor and explanatory multivariate models explained 62-82% of the variance in HbA 1c change, this was mainly associated with baseline HbA 1c (r 2 = 0.544-0.701) and region (r 2 = 0.014-0.037). Other factors were statistically significant but had low predictive power (r 2 < 0.010); in the explanatory analysis, this included end-of-study hypoglycemia (insulin-naive group), insulin dose, and health-related quality of life (r 2 < 0.001-0.006, P £ 0.007). CONCLUSIONSMany factors can guide clinicians in predicting the response to starting therapy with insulin analogs, but many are interdependent and thus of poor utility. The factor explaining most of the variance in HbA 1c change is baseline HbA 1c level, with each increase of 1.0%-units (11 mmol/mol) providing a 0.7-0.8%-units (8-9 mmol/mol) greater fall. Other factors do not explain much of the remaining variance, even when including all end-of-trial measures.

Predictors of HbA1c over 4 years in people with type 2 diabetes starting insulin therapies: The CREDIT study

“…Other publications have addressed this issue in randomised controlled trials of insulin regimens [11][12][13], in retrospective studies from electronic prescriber databases [14][15][16] and in observational studies with features in common with our own [7,17,18]. Randomised clinical trials however, are generally restricted to their planned comparison, and are often of short duration.…”

“…They found that baseline factors predictive of HbA1c <7.0% (<53 mmol/mol) were male sex, white race, shorter duration of diabetes, lower baseline HbA1c, metformin use, and no sulphonylurea use. For the studies from electronic prescribers and databases and from observational studies [7,[14][15][16][17][18], baseline factors predictive of HbA1c <7.0% (<53 mmol/mol) identified in at least one study were lower HbA1c (noted in almost all studies), shorter duration of diabetes, being older, male sex, white race, no oral glucose-lowering drugs before starting insulin, a lower insulin dose, short-acting or premix insulin in comparison to other regimens, lower family income, presence of comorbidities (peripheral vascular disease, cancer, obesity, kidney disease; however, there was no association with other microor macrovascular diseases, or with hypertension), less hypoglycaemia before the start of insulin, and a lower BMI. At the end of the observation periods, a lower insulin dose, a better quality of life, no change in oral therapy, and less hypoglycaemia were associated with a greater reduction of HbA1c.…”

“…However, the people in clinical trials are highly selected according to the trial protocol, advised by the more motivated clinicians who agree to participate in trials, while participants are closely monitored in line with a trial protocol. There is less published information about the outcomes of insulin therapy in current clinical practice, and it is often only very short term [7].…”

The Characteristics of Patients whose both Fasting and Postprandial Glucose were Controlled by Once Daily Basal Insulin Monotherapy

“…A recent paper confirming the predictive factors of insulin analog user in 28 different countries reported that a higher baseline A1c was the most powerful predictor for lower final A1c [16], but sub-analysis of Korean patients showed better response in patients who had lower A1c [15]. Our study was conducted to stop all background OHA and initiate and adjust insulin dosage to reach an optimal FPG goal, which differs from studies that added insulin as a background OHA.…”

Comment on Home et al. Predictive and Explanatory Factors of Change in HbA1c in a 24-Week Observational Study of 66,726 People With Type 2 Diabetes Starting Insulin Analogs. Diabetes Care 2014;37:1237–1245

“…We read with interest the results of the A 1 chieve study (1) As the authors correctly stated, previous analyses between studies have noted that baseline HbA 1c level is a strong predictor of response to glucoselowering agents, including insulin. In the A 1 chieve study, it is stated that for each increase of 1.0%-units (11 mmol/mol) of baseline HbA 1c level there was a 0.7-0.8%-units (8-9 mmol/mol) greater fall.…”