scholarly journals Values, preferences and burden of treatment for the initiation of GLP-1 receptor agonists and SGLT-2 inhibitors in adult patients with type 2 diabetes: a systematic review

BMJ Open ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. e049130
Author(s):  
José Gerardo González-González ◽  
Alejandro Díaz González-Colmenero ◽  
Juan Manuel Millán-Alanís ◽  
Lyubov Lytvyn ◽  
Ricardo Cesar Solis ◽  
...  

ObjectivesAssess values, preferences and burden of treatment that patients with type 2 diabetes consider when initiating glucagon-like peptide-1 receptor agonists (GLP-1 RA) or sodium-glucose cotransporter-2 inhibitors (SGLT-2i) compared with other glucose-lowering options.MethodsPaired reviewers independently included studies reporting quantitative or qualitative methods to assess values, preferences and burden of treatment reported by patients with type 2 diabetes regarding the initiation of GLP-1 RA or SGLT-2i over other alternatives. A systematic search in MEDLINE, Scopus, EMBASE, Web of Science and Cochrane Central Register of Controlled Trials from inception until May 2020 was performed by an experienced librarian. Risk of bias was assessed with a specifically designed tool for values and preferences studies.Results17 studies (7296 patients) proved eligible. Studies fulfilling criteria for SGLT-2i were not identified. Five studies (2662 patients) evaluated preferences for GLP-1 RA compared with other glucose-lowering medications. 12 studies (4634 patients) evaluated preferences between, at least, two kinds of GLP-1 RA or their injection devices based on the following attributes: efficacy, dose, application frequency, device characteristics. Among studies comparing GLP-1 RA to other glucose-lowering medications, some preferences were observed for dypeptil peptidase-4 inhibitors compared with once daily liraglutide. Comparing different attributes of GLP-1 RA drugs and devices, cardiovascular risk reduction, glucose lowering potential, once weekly and simple administered regimens were the most preferred.ConclusionsAs no evidence for preferences on SGLT-2i was available, only preferences for GLP-1 RA were assessed; however, evidence is still limited for the latter. Studies comparing preferences for GLP1-RA to other glucose-lowering alternatives only included twice daily or once daily injection regimens of GLP-1 RA drugs. According to our findings, once weekly alternatives are widely preferred than the formers. The extent to which patients with type 2 diabetes value reduced adverse cardiovascular and kidney outcomes, weighed benefits against harms and burden of treatment is limited and with very low certainty.PROSPERO registration numberCRD42020159284.

2017 ◽  
Vol 125 (07) ◽  
pp. 419-435 ◽  
Author(s):  
Lawrence Leiter ◽  
Michael Nauck

AbstractFor patients with type 2 diabetes mellitus, glucagon-like peptide-1 receptor agonists (GLP-1RAs) generally exert robust glucose-lowering effects that are at least as effective as insulin. As monotherapies, changes from baseline in HbA1c with GLP-1RAs ranged from –1.9 to –0.7% in phase 3 trials. In addition, GLP-1RAs confer a low risk of hypoglycaemia and have a body-weight advantage (changes from baseline ranging from –4.0 to –0.4 kg). There is also evidence of significant reductions in risk for cardiovascular events with some of these agents, with a number of other trials underway. Gastrointestinal adverse events typically increase with GLP-1RAs, although these are generally mild to moderate in intensity and rarely require treatment discontinuation. The GLP-1RAs that are commercially available or in development vary in structure and pharmacokinetics. These differences affect the frequency of administration and can also affect their relative efficacy and safety. This review summarizes the findings of phase 3 glycaemic control trials of available GLP-1RAs and considers them in the context of the distinct clinical needs of individual patients.


2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Feng Sun ◽  
Sanbao Chai ◽  
Lishi Li ◽  
Kai Yu ◽  
Zhirong Yang ◽  
...  

To evaluate the effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on weight reduction in patients with Type 2 diabetes mellitus (Type 2 DM), a network meta-analysis was conducted. MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov were searched from 1950 to October 2013. Randomized controlled trials (RCTs) involving GLP-1 RAs were included if they provided information on body weight. A total of 51 RCTs were included and 17521 participants were enrolled. The mean duration of 51 RCTs was 31 weeks. Exenatide 10 μg twice daily (EX10BID) reduced weight compared with exenatide 5 μg twice daily (EX5BID), liraglutide 0.6 mg once daily (LIR0.6QD), liraglutide—1.2 mg once daily (LIR1.2QD), and placebo treatment, with mean differences of −1.07 kg (95% CI: −2.41, −0.02), −2.38 kg (95% CI: −3.71, −1.06), −1.62 kg (95% CI: −2.79, −0.43), and −1.92 kg (95% CI: −2.61, −1.24), respectively. Reductions of weight treated with liraglutide—1.8 mg once daily (LIR1.8QD) reach statistical significance (−1.43 kg (95% CI: −2.73, −0.15)) versus LIR1.2QD and (−0.98 kg (95% CI: −1.94, −0.02)) versus placebo. Network meta-analysis found that EX10BID, LIR1.8QD, and EX2QW obtained a higher proportion of patients with weight loss than other traditional hypoglycemic agents. Our results suggest GLP-1 RAs are promising candidates for weight control in comparison with traditional hypoglycemic drugs, and EX10BID, LIR1.8QD, and EX2QW rank the top three drugs.


2021 ◽  
Vol 12 ◽  
Author(s):  
Michael A. Nauck ◽  
Daniel R. Quast

To exclude an excess risk of cardiovascular (CV) events, CV outcomes trials (CVOTs) have assessed the effects of new glucose-lowering therapies, including glucagon-like peptide-1 receptor agonists (GLP-1RAs), in patients with type 2 diabetes and established CV disease or CV risk factors. The CV safety of semaglutide vs. placebo, when added to standard care, was evaluated in the SUSTAIN 6 trial for the formulation administered once-weekly subcutaneously and in PIONEER 6 for the new once-daily oral formulation. In SUSTAIN 6 and PIONEER 6, both powered to demonstrate noninferiority (upper 95% confidence interval [CI] of the hazard ratio [HR] <1.8), there were fewer first major adverse CV events with semaglutide vs. placebo, with HRs of 0.74 (95% CI 0.58–0.95) and 0.79 (0.57–1.11), respectively. In SUSTAIN 6, the results were significant for noninferiority and superiority, although the latter was not prespecified. Surprisingly, CV and all-cause mortality were significantly reduced by oral semaglutide in PIONEER 6. The ongoing SOUL CVOT will further inform about CV outcomes with oral semaglutide vs. placebo (NCT03914326). Findings from SUSTAIN 6 and PIONEER 6 fall within the spectrum reported with other GLP-1RA CVOTs: noninferiority vs. placebo for major CV events was seen with lixisenatide and exenatide extended-release, while superiority was demonstrated with liraglutide, albiglutide, and dulaglutide. Beneficial outcomes have been recognized in international guidelines, which recommend subcutaneous liraglutide, semaglutide, and dulaglutide to reduce the risk of CV events in high-risk patients. Both indirect mechanisms via risk factor modification and direct effects via GLP-1 receptors in the CV system have been proposed to be responsible for CV event reductions. The exact mechanism(s) remains to be characterized, but appears to be mainly linked to anti-atherosclerotic effects. Further research is needed to elucidate the relevant mechanisms for CV benefits of GLP-1RAs.


Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1096-P
Author(s):  
RUTH E. BROWN ◽  
ALEXANDER ABITBOL ◽  
HARPREET S. BAJAJ ◽  
HASNAIN KHANDWALA ◽  
RONALD GOLDENBERG ◽  
...  

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1019-P
Author(s):  
YUKI FUJITA ◽  
SODAI KUBOTA ◽  
HITOSHI KUWATA ◽  
DAISUKE YABE ◽  
YOSHIYUKI HAMAMOTO ◽  
...  

2020 ◽  
Vol 98 (3) ◽  
pp. 210-217
Author(s):  
A. Yu. Babenko ◽  
Yu. A. Kononova ◽  
M. V. Martjanova ◽  
A. V. Simanenkova ◽  
M. A. Kokina ◽  
...  

Due to the high efficiency of glucagon-like peptide-1 (GLP-1) receptor agonists therapy in only a part of patients, the search for predictors of response to the treatment is a relevant problem. Purpose. The purpose is to compare the efficacy of liraglutide and exenatide therapy in obese patients with type 2 diabetes mellitus (T2DM) and to evaluate the predictors of response to glycated hemoglobin (HbA1c), weight and lipids reduction. Material and methods. The study included 47 patients with type 2 diabetes and obesity who received GLP-1 receptor agonists therapy. 26 patients were treated with liraglutide, 21 patients were treated with exenatide. We measured the parameters of carbohydrate and lipid metabolism, the levels of hormones involved in glucose and lipids metabolism and in appetite regulation. Blood pressure was measured. These parameters were evaluated at baseline and after 24 weeks of treatment. Results. Patients receiving exenatide therapy showed a tendency towards more frequent HbA1c level reduction by 1% or more (60% versus 30.4%, p = 0.07). The effects of liraglutide and exenatide on weight and waist circumference were comparable. When assessing the predictors of response to the therapy, a more pronounced decrease in HbA1c level (by 1% or more) was in the patients with a higher initial HbA1c level (8.7 (8.2; 9.7) versus 8.2 (6.9; 8.7)%, p = 0.04), as well as with a higher initial GLP-1 level (0.12 (0.05; 0.17) versus 0.040 (0.01; 0.09) ng/ml.) A more significant decrease in the triglycerides (TG) level was detected in patients with a higher level of glucose-dependent insulinotropic peptide (GIP) before therapy (409 (316.0; 431.4) pg/ml in patients who reduced TG level by 30% or more and 331.5 (324.9; 367.1) pg/ml in patients with a lower decrease in TG level). Among the studied parameters, no predictors of body mass reduction were revealed. Conclusion. Measurement of HbA1c, GLP-1, GIP level may be useful to predict the efficacy of GLP-1 receptor agonists therapy.


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