Impact of Glucagon-like Peptide 1 Receptor Agonists on Body Weight in People with HIV and Diabetes Treated with Integrase Inhibitors
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Patient Selection
2.2. Statistical Analyses
3. Results
3.1. Patient Characteristics
3.2. Pharmacologic Therapies
3.3. Effect of GLP1-RAs on Body Weight
3.4. Effects of GLP1-RAs on Other Metabolic Parameters
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
ARV | Antiretroviral therapy |
BMI | Body mass index |
DM | Diabetes mellitus |
GLPI-RA | Glucagon-like peptide-1 receptor agonists |
HBA1c | Glycosylated hemoglobin |
LDL | Low-density lipoprotein |
PWH | People with HIV |
PWHD | People with HIV and diabetes |
TAF | Tenofovir alafenamide |
References
- Schou, M.D.; Søgaard, O.S.; Rasmussen, T.A. Clinical trials aimed at HIV cure or remission: New pathways and lessons learned. Expert Rev. Anti-Infect. Ther. 2023, 21, 1227–1243. [Google Scholar] [CrossRef]
- Collini, P.; Mawson, R.L. A new era of HIV care for age-associated multimorbidity. Curr. Opin. Infect. Dis. 2023, 36, 9–14. [Google Scholar] [CrossRef] [PubMed]
- Daultrey, H.; Levett, T.; Oliver, N.; Vera, J.; Chakera, A.J. HIV and type 2 diabetes: An evolving story. HIV Med. 2024, 25, 409–423. [Google Scholar] [CrossRef] [PubMed]
- Bailin, S.S.; Koethe, J.R. Diabetes in HIV: The Link to Weight Gain. Curr. HIV/AIDS Rep. 2023, 20, 9–18. [Google Scholar] [CrossRef] [PubMed]
- Summers, N.A.; Lahiri, C.D.; Angert, C.D.; Aldredge, A.; Mehta, C.C.; Ofotokun, I.; Kerchberger, A.M.; Gustafson, D.; Weiser, S.D.; Kassaye, S.; et al. Metabolic Changes Associated With the Use of Integrase Strand Transfer Inhibitors Among Virally Controlled Women. J. Acquir. Immune Defic. Syndr. 2020, 85, 355–362. [Google Scholar] [CrossRef]
- .Valenzuela-Rodriguez, G.; Diaz-Arocutipa, C.; Collins, J.A.; Hernandez, A.V. Weight and Metabolic Outcomes in Naïve HIV Patients Treated with Integrase Inhibitor-Based Antiretroviral Therapy: A Systematic Review and Meta-Analysis. J. Clin. Med. 2023, 12, 3644. [Google Scholar] [CrossRef]
- Kanters, S.; Renaud, F.; Rangaraj, A.; Zhang, K.; Limbrick-Oldfield, E.; Hughes, M.; Ford, N.; Vitoria, M. Evidence synthesis evaluating body weight gain among people treating HIV with antiretroviral therapy—A systematic literature review and network meta-analysis. EClinicalMedicine 2022, 48, 101412. [Google Scholar] [CrossRef]
- Capeau, J.; Lagathu, C.; Béréziat, V. Recent data on the role of antiretroviral therapy in weight gain and obesity in persons living with HIV. Curr. Opin. HIV AIDS 2024, 19, 14–20. [Google Scholar] [CrossRef]
- Dupont, E.; Cyr-Yombi, J. Antiretroviral therapy and weight gain in naive HIV-1 infected patient: A narrative review. Aids Rev. 2022, 24, 122–132. [Google Scholar] [CrossRef]
- Drucker, D.J. Efficacy and Safety of GLP-1 Medicines for Type 2 Diabetes and Obesity. Diabetes Care 2024, 47, 1873–1888. [Google Scholar] [CrossRef]
- Fatima, N.; Anand, A.; Palvia, A.R.; Kaur, A.; A Azeez, G.; Thirunagari, M.; Butt, S.R.R. Efficacy of Different Doses and Forms of the GLP-1 Receptor Agonist Semaglutide in Weight Reduction Among Non-diabetic Obese or Overweight Populations. Cureus 2024, 16, e68786. [Google Scholar] [CrossRef] [PubMed]
- Le, R.; Nguyen, M.T.; Allahwala, M.A.; Psaltis, J.P.; Marathe, C.S.; Marathe, J.A.; Psaltis, P.J. Cardiovascular Protective Properties of GLP-1 Receptor Agonists: More than Just Diabetic and Weight Loss Drugs. J. Clin. Med. 2024, 13, 4674. [Google Scholar] [CrossRef] [PubMed]
- Vahora, I.; Moparthi, K.P.; Al Rushaidi, M.T.; Muddam, M.R.; A Obajeun, O.; Abaza, A.; Jaramillo, A.P.; Idris, F.S.; Shaikh, H.A.; Mohammed, L. Efficacy of Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists for Weight Loss Management in Non-Diabetic Patients. Cureus 2024, 16, e65050. [Google Scholar] [CrossRef]
- Jensterle, M.; Rizzo, M.; Haluzík, M.; Janež, A. Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review. Adv. Ther. 2022, 39, 2452–2467. [Google Scholar] [CrossRef]
- Eckard, A.R.; Wu, Q.; Sattar, A.; Ansari-Gilani, K.; Labbato, D.; Foster, T.; A Fletcher, A.; O Adekunle, R.; A McComsey, G. Once-weekly semaglutide in people with HIV-associated lipohypertrophy: A randomised, double-blind, placebo-controlled phase 2b single-centre clinical trial. Lancet Diabetes Endocrinol. 2024, 12, 523–534. [Google Scholar] [CrossRef]
- Nguyen, Q.; Wooten, D.; Lee, D.; Moreno, M.; Promer, K.; Rajagopal, A.; Tan, M.; Tang, M.; Duren, K.; Yin, J.; et al. Glucagon-like Peptide 1 Receptor Agonists Promote Weight Loss Among People With HIV. Clin. Infect. Dis. 2024, 79, 978–982. [Google Scholar] [CrossRef]
- Haidar, L.; Crane, H.M.; Nance, R.M.; Webel, A.; Ruderman, S.A.; Whitney, B.M.; Willig, A.L.; Napravnik, S.; Mixson, L.S.; Leong, C.; et al. Weight loss associated with semaglutide treatment among people with HIV. AIDS 2024, 38, 531–535. [Google Scholar] [CrossRef]
- Savinelli, S.; Newman, E.; Mallon, P.W.G. Metabolic Complications Associated with Use of Integrase Strand Transfer Inhibitors (InSTI) for the Treatment of HIV-1 Infection: Focus on Weight Changes, Lipids, Glucose and Bone Metabolism. Curr. HIV/AIDS Rep. 2024, 21, 293–308. [Google Scholar] [CrossRef]
- Rupasinghe, D.; Bansi-Matharu, L.; Law, M.; Zangerle, R.; Rauch, A.; Tarr, P.E.; Greenberg, L.; Neesgaard, B.; Jaschinski, N.; De Wit, S.; et al. Integrase Strand Transfer Inhibitor-Related Changes in Body Mass Index and Risk of Diabetes: A Prospective Study From the RESPOND Cohort Consortium. Clin. Infect. Dis. 2025, 80, 404–416. [Google Scholar] [CrossRef]
- Gorwood, J.; Bourgeois, C.; Pourcher, V.; Pourcher, G.; Charlotte, F.; Mantecon, M.; Rose, C.; Morichon, R.; Atlan, M.; Le Grand, R.; et al. The Integrase Inhibitors Dolutegravir and Raltegravir Exert Proadipogenic and Profibrotic Effects and Induce Insulin Resistance in Human/Simian Adipose Tissue and Human Adipocytes. Clin. Infect. Dis. 2020, 71, e549–e560. [Google Scholar] [CrossRef]
- Ayissi, K.N.; Gorwood, J.; Le Pelletier, L.; Bourgeois, C.; Beaupère, C.; Auclair, M.; Foresti, R.; Motterlini, R.; Atlan, M.; Barrail-Tran, A.; et al. Inhibition of Adipose Tissue Beiging by HIV Integrase Inhibitors, Dolutegravir and Bictegravir, Is Associated with Adipocyte Hypertrophy, Hypoxia, Elevated Fibrosis, and Insulin Resistance in Simian Adipose Tissue and Human Adipocytes. Cells 2022, 11, 1841. [Google Scholar] [CrossRef] [PubMed]
- Perna, A.; Carleo, M.A.; Mascolo, S.; Guida, A.; Contieri, M.; Sellitto, C.; Hay, E.; De Blasiis, P.; Lucariello, A.; Guerra, G.; et al. Adipocyte differentiation of 3T3-L1 cells under tenofovir alafenamide, tenofovir disoproxil fumarate, and integrase strand transfer inhibitors selective challenge: An in-vitro model. AIDS 2023, 37, 561–570. [Google Scholar] [CrossRef] [PubMed]
- García-Martínez, P.; Gisbert-Ferrándiz, L.; Álvarez, Á.; Esplugues, J.V.; Blas-García, A. Bictegravir alters glucose tolerance in vivo and causes hepatic mitochondrial dysfunction. Antivir. Res. 2024, 231, 106020. [Google Scholar] [CrossRef] [PubMed]
Characteristics | Data |
---|---|
PWHD, n | 25 |
Females, % | 24% |
Age, years | 65 ± 7 |
Body weight, Kg | 79 ± 11 |
Body mass index, Kg/m2 | 28.1 ± 4.4 |
HIV RNA > 100 copies/mL (%) | 4% |
Concomitant comorbidities, % | 100% |
- dyslipidemia, % | 100% |
- hypertension, % | 88% |
- ischemic cardiomyopathy, % | 24% |
- gout, % | 20% |
- chronic renal insufficiency, % | 16% |
- obesity, % | 16% |
- obstructive chronic bronchitis, % | 16% |
On treatment with integrase inhibitors, % | 100% |
- dolutegravir/lamivudine, % | 24% |
- bictegravir/TAF/emtricitabine, % | 20% |
- dolutegravir/abacavir/lamivudine, % | 16% |
- dolutegravir/rilpivirine, % | 16% |
- raltegravir based ARVs, % | 16% |
- others, % | 12% |
Treatment with GLP1-RAs | |
- dulaglutide (0.75–1.5 mg/w), % | 52% |
- exenatide, % | 8% |
- liraglutide (0.6–1.8 mg/day), % | 8% |
- semaglutide tablets (3–7 mg/w), % | 20% |
- semaglutide sc. injection (0.25–0.5 mg/w), % | 12% |
On treatment with other antihyperglycemics, % | 96% |
- metformin, % | 40% |
- insulin + gliflozin, % | 12% |
- metformin + gliflozin, % | 8% |
- metformin + insulin, % | 8% |
- gliflozin, % | 8% |
- glitazon, % | 8% |
- others, % | 16% |
Baseline | Visit 1 | Visit 2 | Visit 3 | Visit 4 | Visit 5 | |
---|---|---|---|---|---|---|
PWHD, n | 25 | 25 | 16 | 10 | 5 | 3 |
Days on GLP1-RA | - | 229 ± 117 | 540 ± 223 | 1052 ± 368 | 1476 ± 493 | 2221 ± 484 |
Body weight (BW), Kg | 80.8 ± 10.7 | 79.8 ± 11.1 | 80.0 ± 7.9 | 80.8 ± 6.8 | 76.8 ± 6.5 | 75.7 ± 8.3 |
Delta BW, Kg * | - | −1.9 ± 3.0 | −4.3 ± 8.9 | −4.6 ± 10.6 | 1.2 ± 7.5 | 2.3 ± 10.1 |
Delta BW, % * | - | −2.2 ± 3.7 | −4.3 ± 8.7 | −3.9 ± 11.4 | 2.5 ± 11.7 | 4.5 ± 15.7 |
Serum glucose, mg/dL | 175 ± 51 | 138 ± 42 ** | 157 ± 68 | 132 ± 23 * | 132 ± 23 | 125 ± 62 |
HbA1c, mmol/L | 59 ± 16 | 49 ± 15 * | 48 ± 12 | 42 ± 8 * | 50 ± 8 | 51 ± 1 |
LDL, mg/dL | 96 ± 43 | 78 ± 26 | 89 ± 30 | 93 ± 17 | 92 ± 35 | 89 ± 8 |
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Cattaneo, D.; Ridolfo, A.L.; Giacomelli, A.; Cossu, M.V.; Dolci, A.; Gori, A.; Antinori, S.; Gervasoni, C. Impact of Glucagon-like Peptide 1 Receptor Agonists on Body Weight in People with HIV and Diabetes Treated with Integrase Inhibitors. Diabetology 2025, 6, 20. https://doi.org/10.3390/diabetology6030020
Cattaneo D, Ridolfo AL, Giacomelli A, Cossu MV, Dolci A, Gori A, Antinori S, Gervasoni C. Impact of Glucagon-like Peptide 1 Receptor Agonists on Body Weight in People with HIV and Diabetes Treated with Integrase Inhibitors. Diabetology. 2025; 6(3):20. https://doi.org/10.3390/diabetology6030020
Chicago/Turabian StyleCattaneo, Dario, Anna Lisa Ridolfo, Andrea Giacomelli, Maria Vittoria Cossu, Alberto Dolci, Andrea Gori, Spinello Antinori, and Cristina Gervasoni. 2025. "Impact of Glucagon-like Peptide 1 Receptor Agonists on Body Weight in People with HIV and Diabetes Treated with Integrase Inhibitors" Diabetology 6, no. 3: 20. https://doi.org/10.3390/diabetology6030020
APA StyleCattaneo, D., Ridolfo, A. L., Giacomelli, A., Cossu, M. V., Dolci, A., Gori, A., Antinori, S., & Gervasoni, C. (2025). Impact of Glucagon-like Peptide 1 Receptor Agonists on Body Weight in People with HIV and Diabetes Treated with Integrase Inhibitors. Diabetology, 6(3), 20. https://doi.org/10.3390/diabetology6030020