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1.
Int J Clin Pract ; 70(3): 218-21, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26916354

ABSTRACT

BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists are an established treatment for people with type 2 diabetes (T2D). We aimed to indirectly compare two GLP-1 receptor agonists, once weekly dulaglutide 1.5 mg and once daily liraglutide 1.8 mg, as a part of clinical trial planning. METHODS: Studies for inclusion in the network meta-analysis (NMA) included all available dulaglutide and liraglutide data as of November 2011 as well as results from the exenatide once weekly registration programme. Change from baseline in haemoglobin A1c (A1c) was the primary endpoint, and a 26-week treatment effect was estimated. RESULTS: Data for 7135 people with T2D from 15 randomised controlled trials (RCTs) followed for 12-52 weeks were included in the quantitative analysis. Observed results from the NMA predicted an A1c change from baseline of -15.1 mmol/mol (-1.38%) in the dulaglutide 1.5 mg group and -14.7 mmol/mol (-1.34%) in the liraglutide 1.8 mg group, with a predicted treatment difference (dulaglutide-liraglutide) of -0.4 mmol/mol (-0.04%) [95% credible interval: -2.4 to 1.5 mmol/mol (-0.22% to 0.14%)]. CONCLUSIONS: The subsequent RCT primary result of a -0.7 mmol/mol (-0.06%) treatment difference (dulaglutide-liraglutide) in A1c demonstrated that once weekly dulaglutide 1.5 mg and once daily liraglutide 1.8 mg resulted in similar glycaemic control, which was consistent with the NMA-predicted treatment difference. NMA is a useful tool and should be considered during clinical trial planning.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Glucagon-Like Peptides/analogs & derivatives , Hypoglycemic Agents/administration & dosage , Immunoglobulin Fc Fragments/administration & dosage , Liraglutide/administration & dosage , Peptides/administration & dosage , Recombinant Fusion Proteins/administration & dosage , Venoms/administration & dosage , Drug Administration Schedule , Exenatide , Glucagon-Like Peptides/administration & dosage , Humans , Network Meta-Analysis , Treatment Outcome
2.
Diabetes Obes Metab ; 18(5): 475-82, 2016 May.
Article in English | MEDLINE | ID: mdl-26799540

ABSTRACT

AIMS: To evaluate the safety and efficacy of once-weekly dulaglutide 1.5 mg, a long-acting glucagon-like peptide-1 receptor agonist, compared with placebo in patients with type 2 diabetes (T2D) on glimepiride monotherapy. METHODS: This phase III, randomized (4 : 1; dulaglutide:placebo), double-blind, placebo-controlled, 24-week study compared the safety and efficacy of once-weekly dulaglutide 1.5 mg with placebo in sulphonylurea-treated (≥half-maximal dose, stable ≥3 months) patients (N = 300) with T2D and inadequate glycaemic control [glycated haemoglobin (HbA1c) ≥7.5 and ≤9.5% (≥58 mmol/mol and ≤80 mmol/mol)]. Analysis was carried out according to intention-to-treat. RESULTS: At baseline, the mean participant age was 58 years; mean HbA1c was 8.4% (68 mmol/mol) and mean weight was 85.5 kg. Dulaglutide 1.5 mg was superior to placebo at 24 weeks for HbA1c reduction from baseline with a between-group HbA1c difference of -1.3% [95% confidence interval (CI) -1.6, -1.0] or -14 mmol/mol (95% CI -17, -11); p < 0.001. A greater proportion of participants in the dulaglutide group reached an HbA1c level of <7.0% (53 mmol/mol) compared with placebo (55.3% vs 18.9%; p < 0.001). Dulaglutide significantly decreased fasting serum glucose from baseline compared with placebo (between-group difference -1.86 mmol/l (95% CI -2.58, -1.14) or -33.54 mg/dl (95% CI -46.55, -20.53); p < 0.001. Weight was decreased significantly from baseline in the dulaglutide group (p < 0.001); the between-group difference was not significant. The most common treatment-emergent adverse events for dulaglutide 1.5 mg were gastrointestinal: nausea (10.5%), diarrhoea (8.4%) and eructation (5.9%). Total hypoglycaemia was higher with dulaglutide 1.5 mg vs placebo (2.37 and 0.07 events/participant/year, respectively; p = 0.025). No severe hypoglycaemia was reported. CONCLUSIONS: Once-weekly dulaglutide 1.5 mg had a favourable benefit/risk profile when added to glimepiride monotherapy.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Glucagon-Like Peptide-1 Receptor/agonists , Glucagon-Like Peptides/analogs & derivatives , Hyperglycemia/prevention & control , Hypoglycemic Agents/therapeutic use , Immunoglobulin Fc Fragments/therapeutic use , Recombinant Fusion Proteins/therapeutic use , Sulfonylurea Compounds/therapeutic use , Aged , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/metabolism , Double-Blind Method , Drug Administration Schedule , Drug Resistance , Drug Therapy, Combination/adverse effects , Female , Glucagon-Like Peptide-1 Receptor/metabolism , Glucagon-Like Peptides/administration & dosage , Glucagon-Like Peptides/adverse effects , Glucagon-Like Peptides/therapeutic use , Glycated Hemoglobin/analysis , Humans , Hypoglycemia/chemically induced , Hypoglycemia/prevention & control , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/adverse effects , Immunoglobulin Fc Fragments/administration & dosage , Immunoglobulin Fc Fragments/adverse effects , Injections, Subcutaneous , Intention to Treat Analysis , Male , Middle Aged , Patient Dropouts , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/adverse effects , Sulfonylurea Compounds/adverse effects
3.
Diabetes Obes Metab ; 18(1): 49-55, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26362460

ABSTRACT

AIM: To compare the effectiveness of dulaglutide 1.5 and 0.75 mg with active comparators and placebo with regard to a composite endpoint of glycated haemoglobin (HbA1c), weight and hypoglycaemia, using post hoc analyses. METHODS: A logistic regression analysis was performed on the intention-to-treat population, using data from the last observation carried forward, and the composite endpoint of HbA1c <7.0% (53 mmol/mol), no weight gain (≤0 kg) and no hypoglycaemia (glucose <3.0 mmol/l or severe hypoglycaemia) after 26 weeks for each trial in the AWARD programme separately. RESULTS: At 26 weeks, within each study, 37-58% of patients on dulaglutide 1.5 mg, 27-49% of patients on dulaglutide 0.75 mg, and 9-61% of patients on active comparators achieved the composite endpoint. Significantly more patients reached the composite endpoint with dulaglutide 1.5 mg than with metformin, sitagliptin, exenatide twice daily or insulin glargine: odds ratio (OR) 1.5 [95% confidence interval (CI) 1.0, 2.2; p < 0.05], OR 4.5 (95% CI 3.0, 6.6; p < 0.001), OR 2.6 (95% CI 1.8, 3.7; p < 0.001) and OR 7.4 (95% CI 4.4, 12.6; p < 0.001), respectively, with no difference between dulaglutide 1.5 mg and liraglutide 1.8 mg. In addition, significantly more patients reached the composite endpoint with dulaglutide 0.75 mg than with sitagliptin or insulin glargine: OR 3.3 (95% CI 2.2, 4.8; p < 0.001) and OR 4.5 (95% CI 2.7, 7.8; p < 0.001), respectively. CONCLUSIONS: Dulaglutide is an effective treatment option, resulting in a similar or greater proportion of patients reaching the HbA1c target of <7.0% (53 mmol/mol), without weight gain or hypoglycaemia compared with active comparators.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Glucagon-Like Peptides/analogs & derivatives , Glycated Hemoglobin/drug effects , Hypoglycemic Agents/administration & dosage , Immunoglobulin Fc Fragments/administration & dosage , Recombinant Fusion Proteins/administration & dosage , Weight Gain/drug effects , Diabetes Mellitus, Type 2/blood , Drug Administration Schedule , Exenatide , Female , Glucagon-Like Peptides/administration & dosage , Glycated Hemoglobin/analysis , Humans , Hypoglycemia/chemically induced , Liraglutide/administration & dosage , Male , Metformin/administration & dosage , Middle Aged , Peptides/administration & dosage , Randomized Controlled Trials as Topic , Sitagliptin Phosphate/administration & dosage , Treatment Outcome , Venoms/administration & dosage
4.
Diabet Med ; 26(11): 1147-55, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19929994

ABSTRACT

AIMS: To compare starter insulins in the elderly subgroup of the DURABLE trial 24-week initiation phase. METHODS: In a post-hoc analysis of the > or = 65 years subgroup enrolled in the DURABLE trial, we compared the safety and efficacy of lispro mix 25 (LM25: lispro 25%/insulin lispro protamine suspension 75%), n = 258, vs. glargine, n = 222, added to oral glucose-lowering agents. RESULTS: Baseline glycated hemoglobin (HbA(1c)) was similar (LM25 8.7 +/- 1.2, glargine 8.8 +/- 1.1%, P = 0.612). At 24-weeks, LM25 patients had lower HbA(1c) (7.0 +/- 0.9 vs. 7.3 +/- 0.9%, P < 0.001), greater HbA(1c) reduction (-1.7 +/- 1.2 vs. -1.5 +/- 1.1%, P < 0.001), and more patients reaching HbA(1c) < 7.0% (55.6 vs. 41.0%, P = 0.005). LM25 patients were on more insulin (0.40 +/- 0.19 vs. 0.33 +/- 0.19 u/kg/day, P < 0.001) and experienced more weight gain (3.6 +/- 3.6 vs. 1.8 +/- 3.2 kg, P < 0.001). Additionally, LM25-treated patients reported a higher mean overall hypoglycaemia rate than glargine patients (40.8 +/- 47.6 vs. 31.1 +/- 48.5 episodes/patient/year, P = 0.037), while nocturnal hypoglycaemia rates were similar. Over 24 weeks, incidence of severe hypoglycaemia was higher for LM25 (4.3% vs. 0.9%, P = 0.018); however, by 24-week endpoint incidence was similar (0.8% vs. 0.0%P = 0.125). CONCLUSIONS: In this elderly subgroup post-hoc analysis, LM25 demonstrated a lower endpoint HbA(1c) and a higher % of patients reaching HbA(1c) target of < 7.0%, but with more weight gain and higher rates of hypoglycaemia compared to glargine.


Subject(s)
Blood Glucose/drug effects , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/administration & dosage , Insulin/analogs & derivatives , Administration, Oral , Aged , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/blood , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Therapy, Combination , Female , Glycated Hemoglobin/drug effects , Glycated Hemoglobin/metabolism , Humans , Hypoglycemia/drug therapy , Insulin/administration & dosage , Insulin Glargine , Insulin Lispro , Insulin, Long-Acting , Male , Treatment Outcome , Weight Gain/drug effects
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