Impact of glucagon‐like peptide‐1 receptor agonists on adiponectin concentrations: A meta‐analysis of randomized controlled trials

Simental‐Mendía, Luis E.; Sánchez‐García, Adriana; Linden-Torres, Enrique; Simental‐Mendía, Mario

doi:10.1111/bcp.14855

Cited by 15 publications

(10 citation statements)

References 44 publications

(111 reference statements)

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“…In fact, both in vivo and in vitro studies, have reported that adiponectin deficiency would trigger an increase in osteoclastogenesis, adipogenesis and a reduction in osteogenesis [ 29 ] . This data confirms a recent meta-analysis that evaluated the effects of GLP-1RAs on adiponectin and found that GLP-1RAs were able to increase adiponectin levels [ 30 ]. Although molecular mechanisms underlying the elevation in circulating adiponectin concentrations following GLP1-RAs are yet to be elucidated, higher values of adiponectin may reduce inflammatory cytokines and oxidative stress with positive effects on bone metabolism [ 30 ].…”

Section: Discussionsupporting

confidence: 90%

“…This data confirms a recent meta-analysis that evaluated the effects of GLP-1RAs on adiponectin and found that GLP-1RAs were able to increase adiponectin levels [ 30 ]. Although molecular mechanisms underlying the elevation in circulating adiponectin concentrations following GLP1-RAs are yet to be elucidated, higher values of adiponectin may reduce inflammatory cytokines and oxidative stress with positive effects on bone metabolism [ 30 ]. However, the relationships between adiponectin levels and BMD values in humans are complex and requires further studies.…”

Section: Discussionsupporting

confidence: 90%

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Glucagon-like Peptide-1 Receptor Agonists and Diabetic Osteopathy: Another Positive Effect of Incretines? A 12 Months Longitudinal Study

Al Refaie,

Baldassini,

Mondillo

et al. 2024

Calcif Tissue Int

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Diabetic osteopathy is a frequent complication in patients with type 2 diabetes mellitus (T2DM). The association between T2DM and increased fracture risk has led to study the impact of new antidiabetic drugs on bone metabolism. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are incretin mimetic drugs which have many pleiotropic properties. The relationship between GLP-1RAs and bone is very complex: while in vitro and animal studies have demonstrated a protective effect on bone, human studies are scarce. We led a 12 months longitudinal study evaluating bone changes in 65 patients withT2DM for whom a therapy with GLP-1RAs had been planned. Fifty-four T2DM patients completed the 12-month study period; of them, 30 had been treated with weekly dulaglutide and 24 with weekly semaglutide. One-year therapy with GLP-1RAs resulted in a significant reduction in weight and BMI. Bone mineral density (BMD), bone metabolism, trabecular bone score (TBS), adiponectin, and myostatin were evaluated before and after 12 months of GLP-1RAs therapy. After 12 months of therapy bone turnover markers and adiponectin showed a significant increase, while myostatin values showed a modest but significant reduction. BMD-LS by DXA presented a significant reduction while the reduction in BMD-LS by REMS was not significant and TBS values showed a marginal increase. Both DXA and REMS techniques showed a modest but significant reduction in femoral BMD. In conclusion, the use of GLP-1RAs for 12 months preserves bone quality and reactivates bone turnover. Further studies are needed to confirm whether GLP-1RAs could represent a useful therapeutic option for patients with T2DM and osteoporosis.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 90%

Glucagon-like Peptide-1 Receptor Agonists and Diabetic Osteopathy: Another Positive Effect of Incretines? A 12 Months Longitudinal Study

Al Refaie,

Baldassini,

Mondillo

et al. 2024

Calcif Tissue Int

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“…GLP-1 receptors are widely distributed throughout the body and have multiple biological effects: suppressing appetite, reducing neuroinflammation, regulating blood lipid metabolism and reducing fat deposition ( 31 ). GLP-1 RAs also elevate adiponectin levels and reduce leptin levels which may have a direct effect on lymphedema ( 32 , 33 ). Adiponectin is an adipocyte complement-related protein that exhibits anti-inflammatory properties and is inversely correlated with BMI ( 34 – 38 ).…”

Section: Discussionmentioning

confidence: 99%

GLP-1 receptor agonist as an effective treatment for breast cancer-related lymphedema: a case report

Crowley,

Brown,

Gallagher

et al. 2024

Front. Oncol.

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IntroductionLymphedema is a major public health issue for many women undergoing breast cancer treatment. Although weight loss has been reported to be beneficial in the treatment of lymphedema, no studies to date have examined the use of GLP-1RAs for the treatment of secondary lymphedema. This case report describes a patient who experienced significant resolution of her breast cancer-related lymphedema after initiation of a GLP-1RA for weight loss.Main symptoms and/or important clinical findingsNine months postoperatively the patient developed arm swelling and disability. While on adjuvant chemo and hormonal therapy, her weight increased dramatically and peaked 4 years later. Corresponding to her weight gain was significant worsening of her symptoms.The main diagnoses, therapeutic interventions, and outcomesDue to adjuvant cancer-related weight gain and inability to lose weight with diet and exercise, she was referred for evaluation and diagnosed with lymphedema. The patient started treatment with a Glucagon-like peptide 1 receptor agonist and lost 24% of her body weight over the next 13 months. The improvement in her lymphedema mirrored her weight loss. Her limb volume difference dropped from 10.3% down to 3.4% and she no longer required a compression garment. Her imaging demonstrated return of lymphatic pumping and she experienced a significant improvement in quality of life, assessed by a validated lymphedema-specific patient reported outcome (PROM). She remains on hormonal therapy, no longer needs compression and is back to regular exercise without impairment.ConclusionsGLP-1 RAs provide a potential medical option for many patients struggling with weight gain and lymphedema. We have observed by all objective measures a significant reduction in lymphedema and the elimination of compression in the case presented as a direct result of GLP-1 RA. This may also reduce a patient’s BMI to the point where they become a good candidate for lymphovenous bypass or vascularized lymph node transplant when indicated.

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“…Second, strict inclu-sion criteria were applied, and studies with active controls were excluded to reduce the possible source of heterogeneity. This is important because several other antidiabetic medications have also been associated with increased plasma adiponectin, such as the dipeptidyl peptidase-4 (DPP4) inhibitors [44] and glucagon-like peptide-1 receptor agonists (GLP-1 RA) [45]. Inclusion studies with DPP4 inhibitors or GLP-1 RA as controls would confound the findings of the meta-analysis and lead to heterogeneity.…”

Section: Discussionmentioning

confidence: 99%

Influence of Sodium-Glucose Cotransporter-2 Inhibitors on Plasma Adiponectin in Patients with Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials

Wang

Xia

2022

Horm Metab Res

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The influence of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on plasma adiponectin remains not comprehensively evaluated. We performed a meta-analysis to systematically evaluate the effect of SGLT2 inhibitors on plasma level of adiponectin in patients with type 2 diabetes mellitus (T2DM). Randomized controlled trials comparing SGLT-2 inhibitors with non-active controls on plasma adiponectin in T2DM patients were retrieved by search of the Medline (PubMed), Embase, and CENTER (Cochrane Library) databases from inception to April 5, 2022. Study characteristics and outcome data were independently extracted by two authors. A random-effect model by incorporating the potential between-study heterogeneity was used to combine the results. Fourteen studies with 2142 patients contributed to the meta-analysis. Compared to placebo, SGLT-2 inhibitors significantly increased plasma adiponectin [standard mean difference (SMD): 0.35, 95% CI: 0.24 to 0.46, p<0.001] with mild heterogeneity (I2=19%). Predefined subgroup analyses suggested that tofogliflozin (SMD: 0.37, p<0.001), luseogliflozin (SMD: 0.51, p<0.001), and ipragliflozin (SMD: 0.34, p<0.001) were associated with increased adiponectin, but not for dapagliflozin (SMD: 0.14, p 0.26). In addition, SGLT-2 inhibitors were associated with increased adiponectin in studies from Asia (SMD: 0.42, p<0.001), but not in studies from the western countries (SMD: 0.16, p 0.17). Moreover, the increment of adiponectin was more significant in patients with body mass index (BMI)<30 kg/m2 (SMD: 0.46, p<0.001) than that in patients with BMI≤30 kg/m2 (SMD: 0.19, p 0.02, p for subgroup difference 0.01). In conclusion, SGLT-2 inhibitors could significantly increase plasma adiponectin as compared with placebo in T2DM patients.

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Impact of glucagon‐like peptide‐1 receptor agonists on adiponectin concentrations: A meta‐analysis of randomized controlled trials

Cited by 15 publications

References 44 publications

Glucagon-like Peptide-1 Receptor Agonists and Diabetic Osteopathy: Another Positive Effect of Incretines? A 12 Months Longitudinal Study

Glucagon-like Peptide-1 Receptor Agonists and Diabetic Osteopathy: Another Positive Effect of Incretines? A 12 Months Longitudinal Study

GLP-1 receptor agonist as an effective treatment for breast cancer-related lymphedema: a case report

Influence of Sodium-Glucose Cotransporter-2 Inhibitors on Plasma Adiponectin in Patients with Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials

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