Cardiovascular and metabolic effects of metformin in patients with type 1 diabetes (REMOVAL): a double-blind, randomised, placebo-controlled trial

Petrie, John R.; Chaturvedi, Nishi; Ford, Ian; Tillin, Therese; Hramiak, Irene; Hughes, Alun D.; Klein, Barbara E.K.; Klein, Ronald; Ooi, Teik Chye; Rossing, Peter; Stehouwer, Coen D. A.; Sattar, Naveed; Colhoun, Helen M.; Nickerson, Helen D.; Lou, Olivia; Dutta, Sanjoy; Haw, Jonathan; Anderson, Caroline; Kean, Sharon; Thomson, Erin; Gibb, James; Greenlaw, Nicola; Keech, Anthony; Jenkins, Alicia J.; March, Katherine; Williams, Scott C.; Coady, Emma; Bots, Michael; Dreyer, Jean-Luc; Jan, T; Sheffy, Koby; Lusky, Ravit; Peleg, S.; Shore, Angela C.; Carty, David; Donnan, Peter T.; Witham, Miles D.; Adler, Andrew; Lonn, Eva; Rauchhaus, Petra; Lindsay, Robert; Brouwers, Martijn C.G.J.; Van‐Melckebeke, J; Gillespie, Louis J.; Hamill, Terence G.; Cuthbertson, Leah; Murray, Andrew; Jolly, Lisa; Miller, Elizabeth R.; Hair, Josie N.; Bell, Alan; Carmichael, Stacy K.; Douglas, Elizabeth; Surtees, Pamela; Dinnett, Eleanor M; Allan, Joseph Joshua; Watson, Chalmers; McLaughlin, Matthew H.; Brindley, Gemma; Smillie, E; Motherwell, D.W.; MacDonald, S; Ellis, Peter; Stuart, Dennis O.; Travers, Mary E.; Brearley, Stephen; Greig, Lynn; Colman, Peter G; Nankervis, Alison; Forulanos, S; West, Daniel J.; Vaughan, Stuart L.; Bjorasen, M; Donlan, John; Vrazas, John; O’Neal, David N; Horsburgh, Jodie C.; Pater, Helen; Kent, Sarah; Twigg, Stephen M.; Fulcher, Gregory; Denner, R; Piotrowicz, A; Januszewski, Andrzej S.; Coy, Andres; Paul, Terri; McDonald, C.F.; Tereschyn, S; Schmidt, Norine; Weingert, M; Heard, H; Burke, Susan J.; Ooi, TC; Lochnan, Heather; Sorisky, Alexander; Keely, Erin; Malcolm, Janine; Maranger, Julie; Favreau, Colette; Petherick, S; Boles, Katrina; Rossing, Peter; Hansen, Tine W.; Lund, Søren S; Hemmingsen, Bianca; Thorogood, Natasha; Green, K; Robinson, Tanisha; Abouglilia, K; Nayman, D; Warren, R. E.; Aizawa, Kunihiko; Balasubramani, M.; Tóth, Štefan; Harvey, Katie; Birch, G. G.; Atkin, Stephen L.; Sathyapalan, Thozhukat; James, Archana; Javed, Zeeshan; Wilding, John; Martin, Barbara K.; Birch, Stephen; Wilcox, A; Watson, Neil; Oliver, Nick; Jugnee, Narvada; Rutter, Martin K; Turgut, Tolga; Shaju, A; Yau, Stephen; Subin, S; Walker, MB; Wake, Dianne; Miller, Clare E.; Millward, Ann; Chong, Pei Nee; Hibbert, Marienne; George, Jacob; Schaper, Nicolaas C.; Pinxt, J; Roodt, J op het; Phillips, Sam; Murray, Lynne; Sleigh, L; Collier, Andrew; Sit, LE; Allan, Karen; Cook, Jennifer; Campbell, Kaitryn; Hodge, L; Leese, Graham; Reekie, G; Jaap, Alan J.; Sudworth, Amanda; White, Alexander; McKnight, John; Steven, L; McKay, Gerard; Llano, Andrea; Currie, Gemma; Lennon, E; Johnstone, Jeanette M.; Shields, Kelly M.

doi:10.1016/s2213-8587(17)30194-8

Cited by 281 publications

(260 citation statements)

References 31 publications

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“…1,2 The REMOVAL study is the largest trial to date that has investigated the longer-term effects of metformin in people with type 1 diabetes. 3 Here, we consider the role of metformin in individuals with type 1 diabetes in light of these results and other study findings.…”

mentioning

confidence: 85%

What role for metformin in type 1 diabetes?

2018

DTB

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Tight glycaemic control is key to reducing the risk of cardiovascular and microvascular complications in people with type 1 diabetes. Standard treatment involves optimising insulin therapy to achieve an HbA level of 48mmol/mol (6.5%) or lower. Although not licensed for use in type 1 diabetes, metformin is included in some clinical guidelines as adjuvant therapy for people with type 1 diabetes who are overweight and wish to improve glycaemic control while minimising the dose of insulin. The REMOVAL study is the largest trial to date that has investigated the longer-term effects of metformin in people with type 1 diabetes. Here, we consider the role of metformin in individuals with type 1 diabetes in light of these results and other study findings.

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mentioning

confidence: 85%

What role for metformin in type 1 diabetes?

2018

DTB

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“…Metformin therapy did not reduce diameter progression (− 0.005 mm per year, 95% CI − 0.012 to 0.002, p = 0.1664) compared with placebo. However, as a secondary outcome, metformin caused a significantly greater reduction in other CVD risk factors such as body weight (− 1.17 kg, 95% CI − 1.66 to − 0.69, p < 0.0001) and LDL-c (− 0.13 mmol/L, − 0.24 to − 0.03; p = 0.0117) as well as an increase in estimated glomerular filtration rate (eGFR) (4.0 mL/min/1.73m 2 , 2.19-5.82, p < 0.0001) [20].…”

Section: Metformin and Cvd Riskmentioning

confidence: 99%

The effect of antidiabetic medications on the cardiovascular system: a critical appraisal of current data

Anagnostis¹,

Siolos²,

Gkekas³

et al. 2018

Hormones

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Both type 1 and type 2 diabetes are associated with increased risk for cardiovascular disease (CVD) events. This risk seems to be reduced by achievement of euglycemia. However, after the withdrawal of rosiglitazone from the market, the question arose as to whether this risk concerns simply a matter of euglycemia or the distinct role played by each antidiabetic drug with respect to its effect on CVD risk. To address this issue, many studies have been published during the last decade involving old and new antidiabetic agents, which however yielded contradictory results. Briefly, metformin is still considered safe and confers a beneficial effect on CVD risk. Conflicting data exist as concerns sulfonylureas, although the second and third generation representatives are regarded as relatively safe. Pioglitazone use seems to be associated with a reduction in CVD risk, whereas the dipeptidyl-dipeptidase-4 inhibitors (DPP-4i), lixisenatide and exenatide-LAR [from the category of glucagon-like-peptide-1 receptor (GLP-1R) agonists], confer a neutral effect. Two other GLP-1R agonists, liraglutide and semaglutide, as well as the sodium-glucose transporter-2 (SGLT2)-inhibitors, empagliflozin and cangliflozin, have shown an additional effect on CVD risk reduction, although their safety is in doubt. Insulin analogues and newer long-acting compounds are also safe for the cadiovascular system. The aim of this narrative review is to present and critically analyse the current data for each antidiabetic drug category with regard to their effect on CVD risk.

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“…Data presented at ADA showed benefits of metformin treatment in these patients, including improved eGFR (p<0.0001), and the EASD session discussed new post hoc analyses which confirmed the original observation and suggest that improved eGFR is due to a direct effect of metformin on the kidney. 9,10 Dr Caroline Day reports from the European Association for the Study of Diabetes 53rd Annual Meeting in Lisbon, Portugal, 11th-15th, September 2017…”

Section: Abstractsmentioning

confidence: 99%

Impressions from EASD 2017

Day

2017

Br J Diabetes

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Cardiovascular and metabolic effects of metformin in patients with type 1 diabetes (REMOVAL): a double-blind, randomised, placebo-controlled trial

Cited by 281 publications

References 31 publications

What role for metformin in type 1 diabetes?

What role for metformin in type 1 diabetes?

The effect of antidiabetic medications on the cardiovascular system: a critical appraisal of current data

Impressions from EASD 2017

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