Semaglutide once weekly in people with type 2 diabetes: Real-world analysis of the Canadian LMC diabetes registry (SPARE study).
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ABSTRACT:
Materials and methods: This study was a retrospective observational study using data from the Canadian LMC Diabetes Registry. Adults with T2D who were naïve to glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy, initiated semaglutide therapy as usual standard of care between February 2018 and February 2019, and maintained semaglutide therapy during follow-up, were eligible for analysis. The primary outcome was mean change in glycated haemoglobin (HbA1c) at 3- to 6-month follow-up.
Results: In the final analytical cohort (n = 937), there was a statistically significant mean?±?SD reduction in HbA1c of -1.03?±?1.24% (11.3 ± 13.6 mmol/mol, P?
Conclusions: This retrospective observational study demonstrated that GLP-1RA-naïve adults with T2D initiating semaglutide in a real-world clinical practice had a statistically and clinically significant reduction in HbA1c and body weight after 3 to 6 months, regardless of semaglutide dose or order of semaglutide therapy, with no significant change in reported incidence of hypoglycaemia.
SUBMITTER: Brown RE
PROVIDER: S-EPMC7689820 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
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Semaglutide once weekly in people with type 2 diabetes: Real-world analysis of the Canadian LMC diabetes registry (SPARE study).
Brown Ruth E RE Bech Peter G PG Aronson Ronnie R
Diabetes, obesity & metabolism 20200713 11
<h4>Aims</h4>To investigate real-world short-term clinical outcomes in adults with type 2 diabetes (T2D) who initiated semaglutide in a specialist endocrinology practice in Canada.<h4>Materials and methods</h4>This study was a retrospective observational study using data from the Canadian LMC Diabetes Registry. Adults with T2D who were naïve to glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy, initiated semaglutide therapy as usual standard of care between February 2018 and February 20 ...[more]
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Project description:IntroductionSURE Netherlands (NCT03929679) evaluated the use of once-weekly (OW) semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1RA), in routine clinical care for individuals with type 2 diabetes (T2D).MethodsAdults (age ≥ 18 years) with T2D were enrolled into the single-arm study. The primary endpoint was change from baseline to end of study (EOS; approx. 30 weeks) in glycated haemoglobin (HbA1c). Secondary endpoints were change from baseline to EOS in body weight (BW) and waist circumference (WC). Proportions of participants achieving predefined HbA1c targets and weight-loss responses at EOS, safety, health-related quality of life (HRQoL) and treatment satisfaction were assessed.ResultsIn total, 211 participants (mean age 60.5 years; diabetes duration 13.3 years) initiated semaglutide; most were receiving metformin (82.9%) and/or basal insulin (59.2%) at baseline, and 6.2% switched from another GLP-1RA. Mean baseline HbA1c, BW and WC were 8.6%, 105.2 kg and 118.8 cm. In the 186 (88.2%) participants receiving semaglutide at EOS, mean reduction in HbA1c with semaglutide was - 1.2%-points (95% [confidence interval] CI - 1.3; - 1.0; p < 0.0001), with 124 (70.5%), 95 (54.0%) and 65 (36.9%) participants achieving HbA1c targets of < 8.0%, < 7.5% and < 7.0%, respectively. Mean reduction in BW was - 7.8 kg [95% CI - 8.7; - 6.8; p < 0.0001], corresponding to relative reduction of - 7.5% [95% CI - 8.4; - 6.6; p < 0.0001]. Improvements in WC (- 8.8 cm [95% CI - 10.4; - 7.2; p < 0.0001]), HRQoL and treatment satisfaction were observed, including across most Short-Form 36 Health Survey domains. One serious adverse drug reaction (cholecystitis) was reported. Eight participants (all receiving concomitant insulin) experienced severe or documented hypoglycaemia.ConclusionIndividuals with T2D treated with OW semaglutide experienced significant and clinically relevant improvements in glycaemic control and BW from baseline. These results from a diverse real-world population in the Netherlands support the use of OW semaglutide in treating adults with T2D in routine clinical practice.
| S-EPMC9768392 | biostudies-literature
Project description:IntroductionOnce-weekly (OW) semaglutide was associated with clinically relevant improvements in glycaemic control and body weight versus comparators in the SUSTAIN randomised controlled trials (RCTs). SURE UK, which is one of a series of individual studies that comprise the SURE programme, evaluated the use of OW semaglutide in a real-world patient population with type 2 diabetes (T2D) in the UK.MethodsIn this prospective, observational study, adults (≥ 18 years) with ≥ 1 documented glycated haemoglobin (HbA1c) value ≤ 12 weeks before semaglutide initiation were enrolled. The primary endpoint was change in HbA1c from baseline to end of study (EOS; ~ 30 weeks, although due to the COVID-19 pandemic, visits up to week 52 were permitted). Secondary endpoints included change in body weight, waist circumference and patient-reported outcomes (PROs). Physicians were to report all episodes of documented or severe hypoglycaemia, fatal events, serious adverse drug reactions, pregnancies and adverse events (AEs) in foetuses/newborn infants; other AEs during the study period could be reported on a voluntary basis.ResultThe estimated mean change in HbA1c from baseline to EOS was - 16.3 mmol/mol [95% confidence interval (CI): - 18.22, - 14.37] (- 1.5%-points [95% CI - 1.67, - 1.31]; p < 0.0001) among the 171 enrolled patients who completed the study on treatment. Mean body weight change was - 5.8 kg (95% CI - 6.75, - 4.94; p < 0.0001). Sensitivity analyses showed similar results. Improvements were also observed in other secondary endpoints, including PROs. No new safety concerns were identified with semaglutide treatment.ConclusionPatients receiving OW semaglutide experienced statistically significant and clinically relevant reductions from baseline in HbA1c and body weight. These results are in line with those of the SUSTAIN RCTs and support the use of OW semaglutide in routine clinical practice in adults with T2D in the UK.Trial registrationClinicalTrials.gov Identifier NCT03876015.
| S-EPMC8475854 | biostudies-literature
Project description:IntroductionThe superior efficacy and safety of semaglutide once-weekly (QW), compared with dulaglutide, liraglutide, or exenatide QW, have been demonstrated in the SUSTAIN trials. This study assessed treatment persistence and adherence to semaglutide QW versus dulaglutide, liraglutide, or exenatide QW in a real-world setting.MethodsThis retrospective, database study used Optum's de-identified Clinformatics® Data Mart Database to identify glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment-naïve adult patients with type 2 diabetes (T2D) initiating semaglutide QW, dulaglutide, liraglutide, or exenatide QW between January 1, 2018 and April 30, 2019. Persistence (time remaining on treatment) was assessed with Kaplan-Meier survival estimates and Cox proportional hazard models. Adherence was assessed using proportion of days covered (PDC) and proportion of patients with PDC > 80%.ResultsOf 56,715 patients included, 3279 received semaglutide QW, 27,891 dulaglutide, 17,186 liraglutide, and 8359 exenatide QW. Patients initiating semaglutide QW were younger and with lower percentage of Medicare coverage than patients initiating the comparators. Persistence at 360 days was significantly higher for semaglutide QW (67.0%) versus dulaglutide (56.0%), liraglutide (40.4%), and exenatide QW (35.5%); p < 0.001 for all comparisons. Compared with semaglutide QW, the discontinuation rate was significantly higher for dulaglutide (hazard ratio [HR] 1.22; 95% confidence interval [CI] 1.13, 1.32; p < 0.001), liraglutide (HR 1.80; 95% CI 1.66, 1.95; p < 0.001), and exenatide QW (HR 2.12; 95% CI 1.96, 2.30; p < 0.001). Adherence to semaglutide QW versus liraglutide at 360 days and to exenatide QW was 39.1% versus 30.0% [p = 0.07] and 27.7% [p = 0.02], respectively. Adherence to dulaglutide at 360 days was numerically higher than semaglutide QW (43.2% versus 39.1%; p = 0.45) but did not reach statistical significance.ConclusionPersistence with semaglutide QW was significantly greater than comparators, while adherence was comparable or greater. Together with earlier results from double-blind clinical studies, these data support semaglutide QW use for treatment of patients with T2D.
| S-EPMC8099966 | biostudies-literature
Project description:AimsTo assess the safety and efficacy of monotherapy with once-weekly subcutaneous (s.c.) semaglutide vs sitagliptin in Japanese people with type 2 diabetes (T2D).MethodsIn this phase IIIa randomized, open-label, parallel-group, active-controlled, multicentre trial, Japanese adults with T2D treated with diet and exercise only or oral antidiabetic drug monotherapy (washed out during the run-in period) received once-weekly s.c. semaglutide (0.5 or 1.0 mg) or once-daily oral sitagliptin 100 mg. The primary endpoint was number of treatment-emergent adverse events (TEAEs) after 30 weeks.ResultsOverall, 308 participants were randomized and exposed to treatment, with similar baseline characteristics across the groups. In total, 2.9% of participants in both the semaglutide 0.5 mg and the sitagliptin group prematurely discontinued treatment, compared with 14.7% in the semaglutide 1.0 mg group. The majority of discontinuations in the semaglutide 0.5 and 1.0 mg groups were attributable to adverse events (AEs). More TEAEs were reported in semaglutide- vs sitagliptin-treated participants (74.8%, 71.6% and 66.0% in the semaglutide 0.5 mg, semaglutide 1.0 mg and sitagliptin groups, respectively). AEs were mainly mild to moderate. Gastrointestinal AEs, most frequently reported with semaglutide, diminished in frequency over time. The mean glycated haemoglobin (HbA1c [baseline 8.1%]) decreased by 1.9% and 2.2% with semaglutide 0.5 and 1.0 mg, respectively, vs 0.7% with sitagliptin (estimated treatment difference [ETD] vs sitagliptin -1.13%, 95% confidence interval [CI] -1.32; -0.94, and -1.44%, 95% CI -1.63; -1.24; both P < .0001). Body weight (baseline 69.3 kg) was reduced by 2.2 and 3.9 kg with semaglutide 0.5 and 1.0 mg, respectively (ETD -2.22 kg, 95% CI -3.02; -1.42 and -3.88 kg, 95% CI -4.70; -3.07; both P < .0001).ConclusionsIn Japanese people with T2D, more TEAEs were reported with semaglutide than with sitagliptin; however, the semaglutide safety profile was similar to that of other glucagon-like peptide-1 receptor agonists. Semaglutide significantly reduced HbA1c and body weight compared with sitagliptin.
| S-EPMC5813234 | biostudies-literature
Project description:OBJECTIVE:The aim of this study was to assess the cost effectiveness of semaglutide versus dulaglutide, as an add-on to metformin monotherapy, for the treatment of type 2 diabetes (T2D), from a Canadian societal perspective. METHODS:The Swedish Institute for Health Economics Cohort Model of T2D was used to assess the cost effectiveness of once-weekly semaglutide (0.5 or 1.0 mg) versus once-weekly dulaglutide (0.75 or 1.5 mg) over a 40-year time horizon. Using data from the SUSTAIN 7 trial, which demonstrated comparatively greater reductions in glycated hemoglobin (HbA1c), body mass index and systolic blood pressure with semaglutide, compared with dulaglutide, a deterministic base-case and scenario simulation were conducted. The robustness of the results was evaluated with probabilistic sensitivity analyses and 15 deterministic sensitivity analyses. RESULTS:The base-case analysis indicated that semaglutide is a dominant treatment option, compared with dulaglutide. Semaglutide was associated with lower total costs (Canadian dollars [CAN$]) versus dulaglutide for both low-dose (CAN$113,287 vs. CAN$113,690; cost-saving: CAN$403) and high-dose (CAN$112,983 vs. CAN$113,695; cost-saving: CAN$711) comparisons. Semaglutide resulted in increased quality-adjusted life-years (QALYs) and QALY gains, compared with dulaglutide, for both low-dose (11.10 vs. 11.07 QALYs; +?0.04 QALYs) and high-dose (11.12 vs. 11.07 QALYs; +?0.05 QALYs) comparisons. The probabilistic sensitivity analysis showed that for 66-73% of iterations, semaglutide was either dominant or was considered cost effective at a willingness-to-pay threshold of CAN$50,000. CONCLUSIONS:From a Canadian societal perspective, semaglutide may be a cost-effective treatment option versus dulaglutide in patients with T2D who are inadequately controlled on metformin monotherapy.
| S-EPMC6861407 | biostudies-literature
Project description:INTRODUCTION:Semaglutide, a new treatment option approved for the treatment of patients with type 2 diabetes mellitus, is a glucagon-like peptide-1 receptor agonist to be injected subcutaneously once weekly. This analysis used a population pharmacokinetic model of semaglutide to identify clinically relevant covariates for exposure. METHODS:A total of 1612 patients with up to seven pharmacokinetic observations each were included in the analysis. All subjects had type 2 diabetes mellitus and were enrolled in one of five trials in the phase III development program for subcutaneous semaglutide once weekly (the SUSTAIN program). The treatment duration of the trials varied from 30 to 104 weeks. RESULTS:No clinically relevant effects on the exposure were seen for sex, age, race, ethnicity, renal function, or injection site used, and semaglutide exposure was stable over time. Of the covariates chosen, only body weight had a relevant effect on the exposure of semaglutide. Few subjects developed semaglutide antibodies, and the antibodies had no effect on exposure. Dose proportionality was shown for the 0.5 mg and 1.0 mg maintenance doses of semaglutide. CONCLUSION:The population pharmacokinetic study showed that semaglutide exposure is not affected by covariates other than body weight at either a maintenance dose of 0.5 or 1.0 mg semaglutide. Therefore, we conclude that no semaglutide dose adjustments are needed in different populations. This finding is to be further explored in an exposure-response analysis. TRIAL REGISTRATION:The trials were registered at ClinicalTrials.gov (identifiers: NCT02054897, NCT01930188, NCT01885208, NCT01720446 and NCT02207374). FUNDING:Novo Nordisk A/S, Bagsværd, Denmark.
| S-EPMC6064581 | biostudies-literature
Project description:BackgroundA once-weekly, 2.4-mg dose of subcutaneous semaglutide, a glucagon-like peptide-1 receptor agonist, is used to treat obesity in adults, but assessment of the drug in adolescents has been lacking.MethodsIn this double-blind, parallel-group, randomized, placebo-controlled trial, we enrolled adolescents (12 to <18 years of age) with obesity (a body-mass index [BMI] in the 95th percentile or higher) or with overweight (a BMI in the 85th percentile or higher) and at least one weight-related coexisting condition. Participants were randomly assigned in a 2:1 ratio to receive once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo for 68 weeks, plus lifestyle intervention. The primary end point was the percentage change in BMI from baseline to week 68; the secondary confirmatory end point was weight loss of at least 5% at week 68.ResultsA total of 201 participants underwent randomization, and 180 (90%) completed treatment. All but one of the participants had obesity. The mean change in BMI from baseline to week 68 was -16.1% with semaglutide and 0.6% with placebo (estimated difference, -16.7 percentage points; 95% confidence interval [CI], -20.3 to -13.2; P<0.001). At week 68, a total of 95 of 131 participants (73%) in the semaglutide group had weight loss of 5% or more, as compared with 11 of 62 participants (18%) in the placebo group (estimated odds ratio, 14.0; 95% CI, 6.3 to 31.0; P<0.001). Reductions in body weight and improvement with respect to cardiometabolic risk factors (waist circumference and levels of glycated hemoglobin, lipids [except high-density lipoprotein cholesterol], and alanine aminotransferase) were greater with semaglutide than with placebo. The incidence of gastrointestinal adverse events was greater with semaglutide than with placebo (62% vs. 42%). Five participants (4%) in the semaglutide group and no participants in the placebo group had cholelithiasis. Serious adverse events were reported in 15 of 133 participants (11%) in the semaglutide group and in 6 of 67 participants (9%) in the placebo group.ConclusionsAmong adolescents with obesity, once-weekly treatment with a 2.4-mg dose of semaglutide plus lifestyle intervention resulted in a greater reduction in BMI than lifestyle intervention alone. (Funded by Novo Nordisk; STEP TEENS ClinicalTrials.gov number, NCT04102189.).
| S-EPMC9997064 | biostudies-literature
Project description:AimsTo investigate real-world clinical outcomes in adults with type 1 diabetes who initiated the Omnipod Insulin Management System (Insulet Corp., Acton, MA, USA) compared to a matched cohort who maintained multiple daily injection therapy.MethodsThis retrospective observational study used data from the Canadian LMC Diabetes Registry. Adults with type 1 diabetes who switched from multiple daily injections to the Omnipod system as usual standard of care between January 2011 and April 2019 were matched to a cohort of adults with type 1 diabetes who maintained multiple daily injection therapy, using propensity-score matching. The primary outcome was change in HbA1c at 3- to 6-month follow-up.ResultsPropensity-score matching resulted in a final analytical cohort of 286 individuals (143/cohort). HbA1c in the Omnipod cohort was reduced by a mean ± sd of -3 ± 10 mmol/mol (-0.2 ± 1.0%; P = 0.005) with no change in the MDI cohort [0 ± 10 mmol/mol (0.0 ± 1.0%); P = 0.74]. HbA1c change was seen only in persons with baseline HbA1c ≥75 mmol/mol (≥9.0%) [Omnipod cohort: -15 ± 12 mmol/mol (-1.4 ± 1.1%); P < 0.001] with a between-treatment difference [mean (95% CI)] of -12 (-18, -6) mmol/mol [-1.1 (-1.6, -0.5) %, P < 0.001]. The median total daily dose of insulin was lower following Omnipod initiation (baseline 0.63 U/kg vs follow-up 0.53 U/kg; P < 0.001), with no change in the MDI cohort (baseline 0.68 U/kg vs follow-up 0.67 U/kg; P = 0.23).ConclusionsAdults with type 1 diabetes who initiated use of the Omnipod system in a real-world clinical setting had lower HbA1c and total daily dose of insulin at 3- to 6-month follow-up compared to a matched cohort of adults who maintained multiple daily injection therapy. A treatment difference in HbA1c change was seen only in people with baseline HbA1c ≥ 75 mmol/mol (9.0%). (Clinical trials registration: NCT04226378).
| S-EPMC8246772 | biostudies-literature
Project description:IntroductionGlucagon-like peptide-1 receptor agonists (GLP-1 RAs) are highly effective for glycaemic control and weight loss in patients with type 2 diabetes (T2D). In this retrospective, observational study, we analysed glycated haemoglobin (HbA1c) and weight following switching to semaglutide from any other GLP-1 RA, using US electronic health records and prescription data.MethodsAdults (≥ 18 years old) with T2D required at least one prescription for injectable semaglutide at index date (treatment switch), at least one prescription for any other GLP-1 RA in the previous 365 days, a baseline HbA1c and/or weight measurement in the 90 days pre-index and a follow-up measurement at 180 and 365 days post-index. HbA1c and weight cohorts were analysed separately using an ANCOVA model. Sensitivity analyses were conducted in patients with at least two prescriptions for pre-switch GLP-1 RA. A secondary analysis compared subgroups receiving different GLP-1 RAs pre-switch.ResultsPatients with HbA1c (n = 710) and weight (n = 921) data had similar baseline characteristics. Significant reductions in HbA1c at 6 months (0.7%; 95% confidence interval [CI] - 0.8, - 0.6) were sustained at 12 months. Weight reductions were significant at 6 months (- 2.1 kg; 95% CI - 2.6, - 1.6) and greater at 12 months (- 2.8 kg; 95% CI - 3.9, - 1.8). These patterns were consistent with the two-prescription sensitivity analysis and independent of the pre-switch GLP-1 RA.ConclusionSwitching to injectable semaglutide from any other GLP-1 RA was associated with significant improvements in glycaemic control and weight. Our findings support decision-making in clinical practice in patients with an indication to switch between GLP-1 RAs.
| S-EPMC7947062 | biostudies-literature
Project description:ObjectiveOur objective was to evaluate the long-term cost-effectiveness of once-weekly semaglutide 1 mg versus once-daily canagliflozin 300 mg in patients with type 2 diabetes mellitus (T2DM) uncontrolled with metformin from the healthcare payer and societal perspectives in Canada.MethodsHead-to-head data from the SUSTAIN 8 randomised trial (NCT03136484) were extrapolated over 40 years using economic simulation modelling. The cost-effectiveness of once-weekly semaglutide 1 mg versus canagliflozin 300 mg for treating T2DM was estimated using the Swedish Institute for Health Economics-Diabetes Cohort Model (IHE-DCM) and the Economic and Health Outcomes Model of T2DM (ECHO-T2DM). Unit costs and disutility weights capturing treatments and key macro- and microvascular complications were sourced from the literature to best match the Canadian setting. A probabilistic base-case simulation and sensitivity analyses were conducted.ResultsOnce-weekly semaglutide 1 mg was associated with reductions in macro- and microvascular complications, yielding incremental cost-effectiveness ratios (ICERs) of (Canadian dollars [CAD]) CAD16,392 and 18,098 per incremental quality-adjusted life-year (QALY) gained versus canagliflozin 300 mg for IHE-DCM and ECHO-T2DM, respectively, from a healthcare payer perspective. Accounting for productivity loss as well, ICERs were CAD14,127 and 13,188 per QALY gained for IHE-DCM and ECHO-T2DM, respectively, from a societal perspective. Sensitivity analyses confirmed that the base-case results were robust to changes in input parameters and assumptions used.ConclusionsAt a willingness-to-pay threshold of CAD50,000 per QALY gained, once-weekly semaglutide 1 mg was cost-effective over 40 years versus once-daily canagliflozin 300 mg for the treatment of T2DM in patients failing to maintain glycemic control with metformin alone.
| S-EPMC9206917 | biostudies-literature