Dulaglutide 1.5 mg as an add‐on option for patients uncontrolled on insulin: Subgroup analysis by age, duration of diabetes and baseline glycated haemoglobin concentration

Abstract

AimsTo assess efficacy and safety of dulaglutide 1.5 mg combined with insulin, categorized by subgroups of baseline glycated haemoglobin (HbA1c; ≤9% and >9% [≤74.9 and >74.9 mmol/mol]), age (<65 and ≥65 years), and duration of diabetes (<10 and ≥10 years) at 6 months in patients with type 2 diabetes (T2D).Materials and methodsThis pooled analysis was conducted in a population of patients with T2D with similar baseline characteristics who were included in the AWARD‐4 and AWARD‐9 clinical trials and randomized to dulaglutide 1.5 mg (pooled mean baseline age 59 years, duration of diabetes 13 years, HbA1c 8.4% [68.3 mmol/mol]). Weight and hypoglycaemia were analysed by individual trial. In AWARD‐4, dulaglutide plus lispro three times daily was assessed against glargine plus lispro three times daily. In AWARD‐9, dulaglutide added to glargine was assessed against placebo added to glargine. Insulins were titrated to target in both trials.ResultsA total of 445 patients were included in this analysis (73% with HbA1c ≤9%, 27% [≤74.9 mmol/mol] with HbA1c >9% [>74.9 mmol/mol]; 70% aged <65 years, 30% aged ≥65 years; 36% with duration of diabetes <10 years, 64% with duration of diabetes ≥10 years). At 6 months, dulaglutide 1.5 mg significantly reduced HbA1c in all subgroups (P < .001), with the highest reduction observed in patients with baseline HbA1c >9% (>74.9 mmol/mol) (range − 1.3% to −2.5% [−14.2 to −27.3 mmol/mol]). The incidence rates of documented symptomatic and severe hypoglycaemia were similar in all subgroups in both trials. The most common adverse events observed in each trial were gastrointestinal in nature.ConclusionDulaglutide 1.5 mg combined with basal or prandial insulin is efficacious for patients with T2D irrespective of age, duration of diabetes or baseline HbA1c.

Impact of baseline characteristics and beta‐cell function on the efficacy and safety of subcutaneous once‐weekly semaglutide: A patient‐level, pooled analysis of the SUSTAIN 1‐5 trials

“…Across the range of baseline HbA1c subgroups in this analysis, subjects with higher HbA1c values at baseline had the greatest reductions in HbA1c , with a statistically significant effect of baseline HbA1c in the semaglutide 1.0 mg treatment arm ( P < 0.05). Baseline HbA1c is a well‐established predictor of glycaemic response for all antidiabetes treatments, even for non‐pharmacological interventions; this finding is consistent with published findings for other GLP‐1RAs, including dulaglutide, liraglutide and lixisenatide . Importantly, from the clinical perspective, these observed differences in the magnitude of change from baseline in HbA1c across HbA1c subgroups resulted in a similar mean end‐of‐treatment HbA1c level.…”

“…Subjects with the highest HbA1c at baseline lost less weight than those with lower HbA1c at baseline, albeit with clinically relevant absolute weight loss. A similar pattern, with less weight loss in subjects with higher baseline HbA1c levels, was also observed with dulaglutide in the AWARD programme, and with liraglutide . These findings may be a result of treatment‐related increases in glycaemic control.…”

“…Furthermore, energy expenditure and resting metabolic rate decrease with weight loss, often accompanied by increased appetite . Contradicting a previous suggestion that modest weight loss in subjects with higher HbA1c may be related to concomitant insulin treatment and accompanying insulin‐related weight gain, the greatest weight loss was observed in these analyses in subjects on a background of basal insulin ± metformin.…”

“…27,28 Furthermore, energy expenditure and resting metabolic rate decrease with weight loss, often accompanied by increased appetite. [27][28][29] Contradicting a previous suggestion that modest weight loss in subjects with higher HbA1c may be related to concomitant insulin treatment and accompanying insulin-related weight gain, 21 Note: %, proportion of subjects experiencing at least one event. Severe or blood glucose-confirmed hypoglycaemia was defined as an episode that was severe according to the ADA classification or blood glucose-confirmed by a plasma glucose value below 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.…”

<p>Dulaglutide as an Add-on to Insulin in Type 2 Diabetes; Clinical Efficacy and Parameters Affecting the Response in Real-World Practice</p>

“…Consistent results have been reported following subgroup analyses of data from clinical trials and observational studies of dulaglutide administration. [15][16][17][18][19][20] In previous studies of the addition of other long-acting GLP-1 RAs, including liraglutide and albiglutide, to insulin, participants with higher baseline HbA1c values also achieved larger reductions in HbA1c. 11,21 In the present analysis, other factors, such as age, sex, baseline body weight, and changes in total daily insulin dose, did not affect the change in HbA1c achieved.…”