Efficacy and tolerability of sodium‐glucose co‐transporter‐2 inhibitors and glucagon‐like peptide‐1 receptor agonists: A systematic review and network meta‐analysis

Hussein, Humaira; Zaccardi, Francesco; Khunti, Kamlesh; Davies, Melanie J.; Patsko, Emily; Dhalwani, Nafeesa N.; Kloecker, David E; Ioannidou, Ekaterini; Gray, Laura J.

doi:10.1111/dom.14008

Cited by 53 publications

(57 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In all, 14 other individuals saw improvements in HbA 1c with the addition of co-therapies. Insulin is an acceptable therapy for type 2 diabetes, but newer agents reduce weight and cardiovascular risk 26,27 and have a reduced risk of hypoglycaemia, need for glucose monitoring and restrictions around driving and employment. Insulin withdrawal was successful in one individual with type 1 diabetes, but in general we were cautious about the use of co-therapies in this group; this is an area that should be addressed in randomised trials.…”

Section: Discussionmentioning

confidence: 99%

Impact of routine clinic measurement of serum C‐peptide in people with a clinician‐diagnosis of type 1 diabetes

et al. 2020

View full text Add to dashboard Cite

The aim of this study was to determine the impact of the routine use of serum C-peptide in an out-patient clinic setting on individuals with a cliniciandiagnosis of type 1 diabetes. Methods: In this single-centre study, individuals with type 1 diabetes of at least 3 years duration were offered random serum C-peptide testing at routine clinic review. A C-peptide ≥200 pmol/L prompted further evaluation of the individual using a diagnostic algorithm that included measurement of islet cell antibodies and genetic testing. Where appropriate, a trial of anti-diabetic co-therapies was considered. Results: Serum C-peptide testing was performed in 859 individuals (90% of the eligible cohort), of whom 114 (13.2%) had C-peptide ≥200 pmol/L. The cause of diabetes was reclassified in 58 individuals (6.8% of the tested cohort). The majority of reclassifications were to type 2 diabetes (44 individuals; 5.1%), with a smaller proportion of monogenic diabetes (14 individuals; 1.6%). Overall, 13 individuals (1.5%) successfully discontinued insulin, while a further 16 individuals (1.9%) had improved glycaemic control following the addition of co-therapies.The estimated total cost of the testing programme was £23,262 (~€26,053), that is, £27 (~€30) per individual tested. In current terms, the cost of prior insulin therapy in the individuals with monogenic diabetes who successfully stopped insulin was approximately £57,000 (~€64,000). Conclusions/interpretation: Serum C-peptide testing can easily be incorporated into an out-patient clinic setting and could be a cost-effective intervention. C-peptide testing should be strongly considered in individuals with a clinician-diagnosis of type 1 diabetes of at least 3 years duration. K E Y W O R D SC-peptide, misclassification, monogenic diabetes, reclassification, type 1 diabetes, type 2 diabetes, type 1 diabetes genetic risk score Click here to access the podcast for this paper. of 1|FOTEINOPOULOU ET aL. F I G U R E 2 Distribution of C-peptide levels by final diagnosis. Data are from the 114 individuals with C-peptide ≥200 pmol/L. Median C-peptide was highest in those reclassified to type 2 diabetes, but there was substantial overlap between the three groups.

show abstract

Section: Discussionmentioning

confidence: 99%

Impact of routine clinic measurement of serum C‐peptide in people with a clinician‐diagnosis of type 1 diabetes

et al. 2020

View full text Add to dashboard Cite

show abstract

“…As far as GLP-1RA treatments are concerned, few RCTs have tested different compounds in head-to-head comparisons, [26][27][28][29][30][31] and often these types of comparison are described by means of network-meta-analyses (ie, using a common comparator as reference, although the studies are conducted in different populations) [32][33][34] or as metaregression. 35,36 However, as described in Table 1, results of RCTs have not always been confirmed in observational studies derived from "real-world" clinical practice.…”

Section: Glycemic and Extra-glycemic Effectiveness Intraclass Comparimentioning

confidence: 99%

“…Despite this need, only a few studies have performed a head-to-head comparison between injectable GLP-1RAs and SGLT2i, 51 with some additional evidence being derived from network meta-analyses. 32,52 As described in Table 3, the overall results from these RCTs have identified a general greater efficacy on HbA1c 53 but not compared with emapagliflozin 54 or canagliflozin. 55,56 The same comparisons have not identified major differences in weight changes between the two classes of drugs.…”

Section: Glp-1ras Vs Sglt2imentioning

confidence: 99%

“…(NWMA) 32 GLP-1RA (Lira and exeOW) > Dapa 53 GLP-1RA = Cana 300 55,56 Body Weight Sema 1.0 mg s.c. > Cana 300 51 No GLP-1RA = Cana 300mg 55,56 Note: The symbol ">" or "<" are used to describe significant higher or lower efficacy or effectiveness between compounds. Abbreviations: Lira, liraglutide; Sema, semaglutide; ExeOW, exenatide-once-weekly; ExeBID, exenatide-bis-in-die; Cana, canagliflozin; Dapa, dapagliflozin; NWMA, network meta-analyses.…”

Section: Effectiveness In Special Populationsmentioning

confidence: 99%

See 1 more Smart Citation

<p>Long-Acting Injectable GLP-1 Receptor Agonists for the Treatment of Adults with Type 2 Diabetes: Perspectives from Clinical Practice</p>

Morieri

Avogaro

Fadini

2020

DMSO

View full text Add to dashboard Cite

Randomized controlled trials (RCTs) have consistently shown glycemic and extra-glycemic benefits of long-acting injectable glucagon-like-peptide-1 receptor agonists (GLP-1RAs, liraglutide, albiglutide, exenatide once-weekly, dulaglutide, and semaglutide) in terms of reduction in the rates of cardiovascular events and mortality among patients with type 2 diabetes. Recently, the analyses of large datasets collecting routinely-accumulated data from clinical practice (ie, real-world studies, RWS) have provided new opportunities to complement the information obtained from RCTs. In this narrative review, we addressed clinically relevant questions that might be answered by well-conducted RWS: are subjects treated with GLP-1RAs in the "real-world" similar to those included in RCTs? Is the performance of GLP-1RA observed in the RWS (effectiveness) similar to that described in RCTs (efficacy)? Is the effectiveness similar in population of patients generally underrepresented in RCTs? Are the cardiovascular benefits of GLP-1RAs confirmed in RWS? We also describe a few comparisons currently un-explored by specific RCTs, such as direct comparison between different administration strategies (eg, fixed-versus flexiblecombination with basal-insulin) or between GLP-1RAs versus dipeptidyl-peptidase-4 inhibitor (DDP4i) or versus sodium/glucose cotransporter-2 inhibitors (SGLT-2i) on hard cardiorenal outcomes. Altogether, RWS provide highly informative information on treatment with GLP-1RAs. On the one side, RWS showed different clinical characteristics between subjects enrolled in RCTs versus those attending real-world clinics and receiving a GLP-1RA. On the other hand, RWS showed that GLP-1RA effectiveness is overall consistent in subgroups of patients less represented in RCTs. In addition, RWS allowed the identification of modifiable factors (eg, titration or adherence) that might guide physicians towards better GLP-1RAs use. Finally, multiple RWS reported better cardio-renal outcomes with GLP-1RAs than with DPP-4i, while initial findings from RWS described a weaker cardiovascular protection compared to SGLT-2i. Therefore, there is the need for further RWS and RCTs comparing these different classes of glucose lowering medications.

show abstract

“…Reductions in body weight were similar between oral semaglutide and empagliflozin in PIONEER 2 after 26 weeks (3.8 versus 3.7 kg, respectively) [21]. A recent network metaanalysis of clinical trials involving GLP-1RAs or SGLT2 inhibitors suggested that long-acting GLP-1RAs, particularly subcutaneous semaglutide, are associated with greater reductions in body weight than SGLT2 inhibitors [28]. No significant differences in body weight reductions were found between oral semaglutide and empagliflozin in PIONEER 2 after 26 or 52 weeks for the treatment policy estimand.…”

Section: Body Weightmentioning

confidence: 91%

Clinical review of the efficacy and safety of oral semaglutide in patients with type 2 diabetes compared with other oral antihyperglycemic agents and placebo

Lavernia

Blonde

2020

Postgraduate Medicine

View full text Add to dashboard Cite

Oral semaglutide is a tablet formulation of a glucagon-like peptide-1 receptor agonist (GLP-1RA), recently approved in the USA and other countries. This paper reviews data from clinical trials (PIONEER 1, 2, 3, and 7) comparing oral semaglutide (once-daily doses of 3, 7, or 14 mg) with either once-daily placebo, empagliflozin 25 mg, or sitagliptin 100 mg. After 26 weeks in PIONEER 1, patients randomized to 3, 7, or 14 mg doses of oral semaglutide monotherapy had statistically significant reductions in glycated hemoglobin (HbA 1c) of 0.9%, 1.2%, and 1.4%, respectively, versus 0.3% with placebo. In the active-comparator studies, oral semaglutide 14 mg provided better glycemic control than empagliflozin or sitagliptin after 26 weeks, with durable effects. Body weight reductions were significantly greater with oral semaglutide than with placebo and sitagliptin. However, body weight reductions with oral semaglutide 14 mg versus empagliflozin 25 mg were not significantly different. Gastrointestinal adverse events (AEs) with oral semaglutide were mostly mild-to-moderate, occurred early in the course of treatment, and abated over time. Across these trials, 5-13% and 15-20% of patients experienced nausea with oral semaglutide 7 and 14 mg, respectively, and 2.3-3.4% and 5.1-8.0%, respectively, discontinued treatment due to gastrointestinal AEs. Severe or blood glucoseconfirmed symptomatic hypoglycemia occurred infrequently with oral semaglutide and was seen most often in patients taking concomitant sulfonylureas. Findings from these trials indicate that the addition of oral semaglutide reduces HbA 1c and body weight and is associated with a low risk of hypoglycemia. Oral semaglutide represents an additional option for treating people with type 2 diabetes in primary care, with the potential to expand the numbers of patients benefiting from GLP-1RAs beyond that currently seen with injectable formulations.

show abstract

Efficacy and tolerability of sodium‐glucose co‐transporter‐2 inhibitors and glucagon‐like peptide‐1 receptor agonists: A systematic review and network meta‐analysis

Abstract: This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as

Cited by 53 publications

References 30 publications

Impact of routine clinic measurement of serum C‐peptide in people with a clinician‐diagnosis of type 1 diabetes

Impact of routine clinic measurement of serum C‐peptide in people with a clinician‐diagnosis of type 1 diabetes

<p>Long-Acting Injectable GLP-1 Receptor Agonists for the Treatment of Adults with Type 2 Diabetes: Perspectives from Clinical Practice</p>

Clinical review of the efficacy and safety of oral semaglutide in patients with type 2 diabetes compared with other oral antihyperglycemic agents and placebo

Contact Info

Product

Resources

About