Exploring the impact of anti-diabetic medications on sarcopenia: a comprehensive review

doi:10.5246/jcps.2024.06.036

Abstract

Abstract:

Sarcopenia is a condition characterized by a reduction in muscle mass and/or diminished muscle function, significantly amplifying the risk of falls, fractures, and even mortality among the elderly. Although diabetes can be further complicated by sarcopenia, the precise cause and mechanism remain unclear. Moreover, the impact of anti-diabetic medications, commonly used by individuals with type 2 diabetes, extends beyond glycemic control. These drugs can influence skeletal muscle through diverse mechanisms, affecting the delicate balance between protein synthesis and breakdown, thereby contributing to the development of sarcopenia. This article delves into the potential mechanisms of anti-diabetic drugs on sarcopenia, offering insights from relevant clinical studies and data.

Key words: Sarcopenia, Anti-diabetic drugs, Skeletal muscle, Diabetes

Supporting:

Litang Tan, Ying Fu. Exploring the impact of anti-diabetic medications on sarcopenia: a comprehensive review[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(6): 481-494.

Figures/Tables 3

References 62

[1]	Kadoguchi, T.; Shimada, K.; Miyazaki, T.; Kitamura, K.; Kunimoto, M.; Aikawa, T.; Sugita, Y.; Ouchi, S.; Shiozawa, T.; Yokoyama-Nishitani, M.; Fukao, K.; Miyosawa, K.; Isoda, K.; Daida, H. Promotion of oxidative stress is associated with mitochondrial dysfunction and muscle atrophy in aging mice. Geriatr. Gerontol. Int. 2019, 20, 78–84.
[2]	Al Saedi, A.; Debruin, D.A.; Hayes, A.; Hamrick, M. Lipid metabolism in sarcopenia. Bone. 2022, 164, 116539.
[3]	Hiromine, Y.; Noso, S.; Rakugi, H.; Sugimoto, K.; Takata, Y.; Katsuya, T.; Fukuda, M.; Akasaka, H.; Osawa, H.; Tabara, Y.; Ikegami, H. Poor glycemic control rather than types of diabetes is a risk factor for sarcopenia in diabetes mellitus: the MUSCLES-DM study. J. Diabetes Investig. 2022, 13, 1881–1888.
[4]	Bhardwaj, G.; Penniman, C.M.; Jena, J.; Suarez Beltran, P.A.; Foster, C.; Poro, K.; Junck, T.L.; Hinton, A.O. Jr, Souvenir, R.; Fuqua, J.D.; Morales, P.E.; Bravo-Sagua, R.; Sivitz, W.I.; Lira, V.A.; Abel, E.D.; O'Neill, B.T. Insulin and IGF-1 receptors regulate complex I-dependent mitochondrial bioenergetics and super complexes via FoxOs in muscle. J. Clin. Invest. 2021, 131, e146415.
[5]	Wang, W.H.; Gu, X.C.; Cao, Z.Y.; Wang, X.J.; Lei, Y.M.; Xu, X.L.; Wang, S.W.; Wu, T.; Bao, Z. A potential correlation between adipokines, skeletal muscle function and bone mineral density in middle-aged and elderly individuals. Lipids Health Dis. 2023, 22, 111.
[6]	Sato, M.; Fujita, H.; Yokoyama, H.; Mikada, A.; Horikawa, Y.; Takahashi, Y.; Yamada, Y.; Waki, H.; Narita, T. Relationships among postprandial plasma active GLP-1 and GIP excursions, skeletal muscle mass, and body fat mass in patients with type 2 diabetes treated with either miglitol, sitagliptin, or their combination: a secondary analysis of the MASTER study. J. Clin. Med. 2023, 12, 3104.
[7]	Sencan, C.; Dost, F.S.; Ates Bulut, E.; Isik, A.T. DPP4 inhibitors as a potential therapeutic option for sarcopenia: a 6-month follow-up study in diabetic older patients. Exp. Gerontol. 2022, 164, 111832.
[8]	Koshizaka, M.; Ishikawa, K.; Ishibashi, R.; Maezawa, Y.; Sakamoto, K.; Uchida, D.; Nakamura, S.; Yamaga, M.; Yokoh, H.; Kobayashi, A.; Onishi, S.; Kobayashi, K.; Ogino, J.; Hashimoto, N.; Tokuyama, H.; Shimada, F.; Ohara, E.; Ishikawa, T.; Shoji, M.; Ide, S.; Ide, K.; Baba, Y.; Hattori, A.; Kitamoto, T.; Horikoshi, T.; Shimofusa, R.; Takahashi, S.; Nagashima, K.; Sato, Y.; Takemoto, M.; Newby, L.K.; Yokote, K.; Group, P.V.S. Effects of ipragliflozin versus metformin in combination with sitagliptin on bone and muscle in Japanese patients with type 2 diabetes mellitus: Subanalysis of a prospective, randomized, controlled study (PRIME-V study). J. Diabetes Investig. 2021, 12, 200–206.
[9]	Ishii, S.; Nagai, Y.; Kato, H.; Fukuda, H.; Tanaka, Y. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin on muscle mass and the muscle/fat ratio in patients with type 2 diabetes. J. Clin. Med. Res. 2020, 12, 122–126.
[10]	Rizzo, M.R.; Barbieri, M.; Marfella, R.; Paolisso, G. Reduction of oxidative stress and inflammation by blunting daily acute glucose fluctuations in patients with type 2 diabetes: role of dipeptidyl peptidase-IV inhibition. Diabetes Care. 2012, 35, 2076–2082.
[11]	Rizzo, M.R.; Barbieri, M.; Fava, I.; Desiderio, M.; Coppola, C.; Marfella, R.; Paolisso, G. Sarcopenia in elderly diabetic patients: role of dipeptidyl peptidase 4 inhibitors. J. Am. Med. Dir. Assoc. 2016, 17, 896–901.
[12]	Zhang, X.L.; Zhao, Y.; Chen, S.B.; Shao, H. Anti-diabetic drugs and sarcopenia: emerging links, mechanistic insights, and clinical implications. J. Cachexia Sarcopenia Muscle. 2021, 12, 1368–1379.
[13]	Mele, A.; Calzolaro, S.; Cannone, G.; Cetrone, M.; Conte, D.; Tricarico, D. Database search of spontaneous reports and pharmacological investigations on the sulfonylureas and glinides-induced atrophy in skeletal muscle. Pharmacol. Res. Perspect. 2014, 2, e00028.
[14]	Schemke, S.; de Wit, C. K_ATP channels and NO dilate redundantly intramuscular arterioles during electrical stimulation of the skeletal muscle in mice. Pflügers Arch. Eur. J. Physiol. 2021, 473, 1795–1806.
[15]	Ma, R.C.W. Acarbose: an alternative to metformin for first-line treatment in type 2 diabetes? Lancet Diabetes Endocrinol. 2014, 2, 6–7.
[16]	Jiang, L.L.; Xu, X.H.; Luo, M.H.; Wang, H.Y.; Ding, B.; Yan, R.N.; Hu, Y.; Ma, J.H. Association of acarbose with decreased muscle mass and function in patients with type 2 diabetes: a retrospective, cross-sectional study. Diabetes Ther. 2021, 12, 2955–2969.
[17]	Zhu, Q.B.; Tong, Y.Z.; Wu, T.X.; Li, J.Q.; Tong, N.W. Comparison of the hypoglycemic effect of acarbose monotherapy in patients with type 2 diabetes mellitus consuming an eastern or western diet: a systematic meta-analysis. Clin. Ther. 2013, 35, 880–899.
[18]	Wolf, V.L.W.; Breder, I.; de Carvalho, L.S.F.; Soares, A.A.S.; Cintra, R.M.; Barreto, J.; Munhoz, D.B.; Kimura-Medorima, S.T.; Nadruz, W.; Guerra-Júnior, G.; Quinaglia, T.; Muscelli, E.; Sposito, A.C.; Investigators, A.B. Dapagliflozin increases the lean-to total mass ratio in type 2 diabetes mellitus. Nutr. Diabetes. 2021, 11, 17.
[19]	Kitazawa, T.; Seino, H.; Ohashi, H.; Inazawa, T.; Inoue, M.; Ai, M.; Fujishiro, M.; Kuroda, H.; Yamada, M.; Anai, M.; Ishihara, H. Comparison of tofogliflozin versus glimepiride as the third oral agent added to metformin plus a dipeptidyl peptidase-4 inhibitor in Japanese patients with type 2 diabetes: a randomized, 24-week, open-label, controlled trial (STOP-OB). Diabetes Obes. Metab. 2020, 22, 1659–1663.
[20]	Sugimoto, K.; Ikegami, H.; Takata, Y.; Katsuya, T.; Fukuda, M.; Akasaka, H.; Tabara, Y.; Osawa, H.; Hiromine, Y.; Rakugi, H. Glycemic control and insulin improve muscle mass and gait speed in type 2 diabetes: the MUSCLES-DM study. J. Am. Med. Dir. Assoc. 2021, 22, 834–838.e1.
[21]	Bouchi, R.; Fukuda, T.; Takeuchi, T.; Nakano, Y.; Murakami, M.; Minami, I.; Izumiyama, H.; Hashimoto, K.; Yoshimoto, T.; Ogawa, Y. Insulin treatment attenuates decline of muscle mass in Japanese patients with type 2 diabetes. Calcif. Tissue Int. 2017, 101, 1–8.
[22]	Ferrari, U.; Then, C.; Rottenkolber, M.; Selte, C.; Seissler, J.; Conzade, R.; Linkohr, B.; Peters, A.; Drey, M.; Thorand, B. Longitudinal association of type 2 diabetes and insulin therapy with muscle parameters in the KORA-Age study. Acta Diabetol. 2020, 57, 1057–1063.
[23]	Imre, E.; Apaydin, T.; Gunhan, H.G.; Yavuz, D.G. Determinants of high-dose insulin usage and upper extremity muscle strength in adult patients with type 2 diabetes. Can. J. Diabetes. 2021, 45, 341–345.
[24]	Krzykała, M.; Domaszewska, K.; Woźniewicz-Dobrzyńska, M.; Kryściak, J.; Konarska, A.; Araszkiewicz, A.; Zozulińska-Ziółkiewicz, D.; Gawrecki, A.; Biegański, G.; Konarski, J.M. Characteristics of selected somatic and motor abilities of youth soccer players with diabetes type 1 treated with insulin pump therapy. Int. J. Environ. Res. Public Health. 2021, 18, 3493.
[25]	Kjøbsted, R.; Hingst, J.R.; Fentz, J.; Foretz, M.; Sanz, M.N.; Pehmøller, C.; Shum, M.; Marette, A.; Mounier, R.; Treebak, J.T.; Wojtaszewski, J.F.P.; Viollet, B.; Lantier, L. AMPK in skeletal muscle function and metabolism. FASEB J. 2018, 32, 1741–1777.
[26]	Senesi, P.; Montesano, A.; Luzi, L.; Codella, R.; Benedini, S.; Terruzzi, I. Metformin treatment prevents sedentariness related damages in mice. J. Diabetes Res. 2016, 2016, 8274689.
[27]	Kanigur Sultuybek, G.; Soydas, T.; Yenmis, G. NF-κB as the mediator of metformin’s effect on ageing and ageing-related diseases. Clin. Exp. Pharmacol. Physiol. 2019, 46, 413–422.
[28]	Petrocelli, J.J.; McKenzie, A.I.; de Hart, N.M.; Reidy, P.; Mahmassani, Z.; Keeble, A.R.; Kaput, K.L.; Wahl, M.P.; Rondina, M.; Marcus, R.; Welt, C.; Holland, W.; Funai, K.; Fry, C.; Drummond, M. Disuse‐induced muscle fibrosis, cellular senescence, and senescence‐associated secretory phenotype in older adults are alleviated during re‐ambulation with metformin pre‐treatment. Aging Cell. 2023, e13936.
[29]	Zhu, Y.Q.; Chen, X.; Geng, S.S.; Li, Q.Q.; Li, Y.; Yuan, H.X.; Jiang, H. Identification of the cuproptosis-related hub genes and therapeutic agents for sarcopenia. Front. Genet. 2023, 14, 1136763.
[30]	Yang, Y.F.; Liao, Z.Y.; Xiao, Q. Metformin ameliorates skeletal muscle atrophy in Grx1 KO mice by regulating intramuscular lipid accumulation and glucose utilization. Biochem. Biophys. Res. Commun. 2020, 533, 1226–1232.
[31]	Ai, Y.Q.; Xu, R.X.; Liu, L.X. The prevalence and risk factors of sarcopenia in patients with type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetol Metab Syndr. 2021, 13, 93.
[32]	Liu, Q.S. Thesis, Tianjin Agricultural University. 2021.
[33]	Kang, M.J.; Moon, J.; Lee, J.O.; Kim, J.H.; Jung, E.J.; Kim, S.J.; Oh, J.Y.; Wu, S.W.; Lee, P.; Park, S.H.; Kim, H.S. Metformin induces muscle atrophy by transcriptional regulation of myostatin via HDAC6 and FoxO3a. J. Cachexia Sarcopenia Muscle. 2022, 13, 605–620.
[34]	McKenzie, A.I.; Mahmassani, Z.S.; Petrocelli, J.J.; de Hart, N.M.M.P.; Fix, D.K.; Ferrara, P.J.; LaStayo, P.C.; Marcus, R.L.; Rondina, M.T.; Summers, S.A.; Johnson, J.M.; Trinity, J.D.; Funai, K.; Drummond, M.J. Short-term exposure to a clinical dose of metformin increases skeletal muscle mitochondrial H₂O₂ emission and production in healthy, older adults: a randomized controlled trial. Exp. Gerontol. 2022, 163, 111804.
[35]	Neumiller J.J.; White J.R.; Campbell, R.K. Sodium-glucose co-transport inhibitors: progress and therapeutic potential in type 2 diabetes mellitus. Drugs. 2010, 70, 377–385.
[36]	Zeng, Y.H.; Liu, S.C.; Lee, C.C.; Sun, F.J.; Liu, J.J. Effect of empagliflozin versus linagliptin on body composition in Asian patients with type 2 diabetes treated with premixed insulin. Sci. Rep. 2022, 12, 17065.
[37]	Han, J.X.; Luo, L.L.; Wang, Y.C.; Miyagishi, M.; Kasim, V.; Wu, S.R. SGLT2 inhibitor empagliflozin promotes revascularization in diabetic mouse hindlimb ischemia by inhibiting ferroptosis. Acta Pharmacol. Sin. 2023, 44, 1161–1174.
[38]	Xie, K.Y.; Sugimoto, K.; Tanaka, M.; Akasaka, H.; Fujimoto, T.; Takahashi, T.; Onishi, Y.; Minami, T.; Yoshida, S.; Takami, Y.; Yamamoto, K.; Rakugi, H. Effects of luseogliflozin treatment on hyperglycemia-induced muscle atrophy in rats. J. Clin. Biochem. Nutr. 2023, 72, 248–255.
[39]	Hata, S.; Okamura, T.; Kobayashi, A.; Bamba, R.; Miyoshi, T.; Nakajima, H.; Kitagawa, N.; Hashimoto, Y.; Majima, S.; Senmaru, T.; Okada, H.; Ushigome, E.; Nakanishi, N.; Takakuwa, H.; Sasano, R.; Hamaguchi, M.; Fukui, M. Gut microbiota changes by an SGLT2 inhibitor, luseogliflozin, alters metabolites compared with those in a low carbohydrate diet in db/db mice. Nutrients. 2022, 14, 3531.
[40]	Wu, H.Z.; Ballantyne, C.M. Skeletal muscle inflammation and insulin resistance in obesity. J. Clin. Investig. 2017, 127, 43–54.
[41]	Sugiyama, S.; Jinnouchi, H.; Kurinami, N.; Hieshima, K.; Yoshida, A.; Jinnouchi, K.; Nishimura, H.; Suzuki, T.; Miyamoto, F.; Kajiwara, K.; Jinnouchi, T. Dapagliflozin reduces fat mass without affecting muscle mass in type 2 diabetes. J. Atheroscler. Thromb. 2018, 25, 467–476.
[42]	Hajime, Y.; Masashi, T.; Takayuki, I.; Shinji, O.; Toru, K.; Noriko, S.A. Effects of dapagliflozin on the serum levels of fibroblast growth factor 21 and myokines and muscle mass in Japanese patients with type 2 diabetes: a randomized, controlled trial. J. Diabetes Investig. 2020, 11, 653–661.
[43]	Nugrahaningrum, D.A.; Marcelina, O.; Liu, C.P.; Wu, S.R.; Kasim, V. Dapagliflozin promotes neovascularization by improving paracrine function of skeletal muscle cells in diabetic hindlimb ischemia mice through PHD2/HIF-1α axis. Front. Pharmacol. 2020, 11, 1104.
[44]	Yasuda, M.; Iizuka, K.; Kato, T.; Liu, Y.Y.; Ken, T.K.; Nonomura, K.; Mizuno, M.; Yabe, D. Sodium-glucose cotransporter 2 inhibitor and sarcopenia in a lean elderly adult with type 2 diabetes: a case report. J. Diabetes Investig. 2020, 11, 745–747.
[45]	Langer, H.T.; Ramsamooj, S.; Dantas, E.; Murthy, A.; Ahmed, M.; Hwang, S.K.; Grover, R.; Pozovskiy, R.; Liang, R.J.; Queiroz, A.L.; Brown, J.C.; White, E.P.; Janowitz, T.; Goncalves, M.D. Restoring adiponectin via rosiglitazone ameliorates tissue wasting in mice with lung cancer. bioRxiv. 2023, DOI: 10.1101/2023.07.31.551241.
[46]	Reusch, J.E.B.; Bridenstine, M.; Regensteiner, J.G. Type 2 diabetes mellitus and exercise impairment. Rev. Endocr. Metab. Disord. 2013, 14, 77–86.
[47]	Reusch, J.E.B.; Regensteiner, J.G.; Watson, P.A. Novel actions of thiazolidinediones on vascular function and exercise capacity. Am. J. Med. 2003, 115, 69–74.
[48]	Bastien, M.; Poirier, P.; Brassard, P.; Arsenault, B.J.; Bertrand, O.F.; Després, J.P.; Costerousse, O.; Piché, M.E. Effect of PPARγ agonist on aerobic exercise capacity in relation to body fat distribution in men with type 2 diabetes mellitus and coronary artery disease: a 1-yr randomized study. Am. J. Physiol. Endocrinol. Metab. 2019, 317, E65–E73.
[49]	McClelland, T.J.; Fowler, A.J.; Davies, T.W.; Pearse, R.; Prowle, J.; Puthucheary, Z. Can Pioglitazone Be Used for Optimization of Nutrition in Critical Illness? A Systematic Review. JPEN. 2023, 47, 459–475.
[50]	Shah, P.K.; Mudaliar, S.; Chang, A.R.; Aroda, V.; Andre, M.; Burke, P.; Henry, R.R. Effects of intensive insulin therapy alone and in combination with pioglitazone on body weight, composition, distribution and liver fat content in patients with type 2 diabetes. Diabetes Obes. Metab. 2011, 13, 505–510.
[51]	Hassan, F.E.; Sakr, H.I.; Mohie, P.M.; Suliman, H.S.; Mohamed, A.S.; Attia, M.H.; Eid, D.M. Pioglitazone improves skeletal muscle functions in reserpine-induced fibromyalgia rat model. Ann. Med. 2021, 53, 1033–1041.
[52]	Fiorentino, T.V.; Monroy, A.; Kamath, S.; Sotero, R.; Cas, M.D.; Daniele, G.; Chavez, A.O.; Abdul-Ghani, M.; Hribal, M.L.; Sesti, G.; Tripathy, D.; DeFronzo, R.A.; Folli, F. Pioglitazone corrects dysregulation of skeletal muscle mitochondrial proteins involved in ATP synthesis in type 2 diabetes. Metabolism. 2021, 114, 154416.
[53]	Yokoyama, I.; Yonekura, K.; Moritan, T.; Tateno, M.; Momose, T.; Ohtomo, K.; Inoue, Y.; Nagai, R. Troglitazone improves whole-body insulin resistance and skeletal muscle glucose use in type II diabetic patients. J. Nucl. Med. 2001, 42, 1005–1010.
[54]	Shibuya, S.; Watanabe, K.; Sakuraba, D.; Abe, T.; Shimizu, T. Natural compounds that enhance motor function in a mouse model of muscle fatigue. Biomedicines. 2022, 10, 3073.
[55]	Fan, D.M.; Wang, Y.; Liu, B.W.; Yin, F. Hypoglycemic drug liraglutide alleviates low muscle mass by inhibiting the expression of MuRF1 and MAFbx in diabetic muscle atrophy. J. Chin. Med. Assoc. 2022, 86, 166–175.
[56]	Uchiyama, S.; Sada, Y.; Mihara, S.; Sasaki, Y.; Sone, M.; Tanaka, Y. Oral semaglutide induces loss of body fat mass without affecting muscle mass in patients with type 2 diabetes. J. Clin. Med. Res. 2023, 15, 377–383.
[57]	Volpe, S.; Lisco, G.; Fanelli, M.; Racaniello, D.; Colaianni, V.; Lavarra, V.; Triggiani, D.; Crudele, L.; Triggiani, V.; Sabbà, C.; De Pergola, G.; Piazzolla, G. Oral semaglutide improves body composition and preserves lean mass in patients with type 2 diabetes: a 26-week prospective real-life study. Front. Endocrinol. 2023, 14, 1240263.
[58]	Keskin, L.; Yaprak, B. Comparison of the effect of liraglutide and metformin therapy on the disease regulation and weight loss in obese patients with Type 2 diabetes mellitus. Eur. Rev. Med. Pharmacol. Sci. 2022, 26, 6813–6820.
[59]	Chen, F.Q.; Xu, S.; Wang, Y.F.; Chen, F.; Cao, L.; Liu, T.T.; Huang, T.; Wei, Q.; Ma, G.J.; Zhao, Y.H.; Wang, D.F. Risk factors for sarcopenia in the elderly with type 2 diabetes mellitus and the effect of metformin. J. Diabetes Res. 2020, 2020, 1–10.
[60]	Veelen, A.; Andriessen, C.; den Kamp, Y.O.; Erazo-Tapia, E.; de Ligt, M.; Mevenkamp, J.; Jörgensen, J.A.; Moonen-Kornips, E.; Schaart, G.; Esterline, R.; Havekes, B.; Oscarsson, J.; Schrauwen-Hinderling, V.B.; Phielix, E.; Schrauwen, P. Effects of the sodium-glucose cotransporter 2 inhibitor dapagliflozin on substrate metabolism in prediabetic insulin resistant individuals: a randomized, double-blind crossover trial. Metabolism. 2023, 140, 155396.
[61]	Op den Kamp, Y.J.M.; Gemmink, A.; de Ligt, M.; Dautzenberg, B.; Kornips, E.; Jorgensen, J.A.; Schaart, G.; Esterline, R.; Pava, D.A.; Hoeks, J.; Schrauwen-Hinderling, V.B.; Kersten, S.; Havekes, B.; Koves, T.R.; Muoio, D.M.; Hesselink, M.K.C.; Oscarsson, J.; Phielix, E.; Schrauwen, P. Effects of SGLT2 inhibitor dapagliflozin in patients with type 2 diabetes on skeletal muscle cellular metabolism. Mol. Metab. 2022, 66, 101620.
[62]	Matsuba, I.; Takihata, M.; Takai, M.; Maeda, H.; Kubota, A.; Iemitsu, K.; Umezawa, S.; Obana, M.; Kaneshiro, M.; Kawata, T.; Takuma, T.; Takeda, H.; Machimura, H.; Mokubo, A.; Motomiya, T.; Asakura, T.; Kikuchi, T.; Matsuzawa, Y.; Ito, S.; Miyakawa, M.; Terauchi, Y.; Kanamori, A. Effects of 1‐year treatment with canagliflozin on body composition and total body water in patients with type 2 diabetes. Diabetes. 2021, 23, 2614–2622.