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18-07-2017 | SGLT2 inhibitors | Review | Article

Practical Approach to Initiating SGLT2 Inhibitors in Type 2 Diabetes

Journal: Diabetes Therapy

Authors: Fernando Gomez-Peralta, Cristina Abreu, Albert Lecube, Diego Bellido, Alfonso Soto, Cristóbal Morales, Miguel Brito-Sanfiel, Guillermo Umpierrez

Publisher: Springer Healthcare

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Abstract

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are an attractive novel therapeutic option for the treatment of type 2 diabetes. They block the reabsorption of filtered glucose in kidneys, mainly in proximal renal tubules, resulting in increased urinary glucose excretion and correction of the diabetes-related hyperglycemia. Beyond improving glucose control, SGLT2 inhibitors offer potential benefits by reducing body weight and blood pressure. On the basis of the efficacy demonstrated in clinical trials, SGLT2 inhibitors are recommended as second- or third-line agents for the management of patients with type 2 diabetes. Beneficial effects on kidney disease progression, cardiovascular and all-cause mortality, and hospitalization for heart failure have also been demonstrated with one SGLT2 inhibitor (empagliflozin). Potential adverse events resulting from their mechanism of action or related to concomitant therapies are reviewed. A treatment algorithm for the adjustment of concomitant therapies after initiating SGLT2 inhibitors is also proposed.
Literature
1.
American Diabetes Association. Standards of medical care in diabetes-2017. Diabetes Care. 2017;40:S1–135.CrossRef
2.
Shah BR, Hux JE, Laupacis A, Zinman B, van Walraven C. Clinical inertia in response to inadequate glycemic control: do specialists differ from primary care physicians? Diabetes Care. 2005;28:600–6.CrossRefPubMed
3.
Inzucchi SE. Oral antihyperglycemic therapy for type 2 diabetes. JAMA. 2002;287:360–72.CrossRefPubMed
4.
Nauck MA. Update on developments with SGLT2 inhibitors in the management of type 2 diabetes. Drug Des Devel Ther. 2014;8:1335–80.CrossRefPubMedPubMedCentral
5.
Fioretto P, Zambon A, Rossato M, Busetto L, Vettor R. SGLT2 inhibitors and the diabetic kidney. Diabetes Care. 2016;39:S165–71.CrossRefPubMed
6.
Bailey CJ, Gross JL, Pieters A, Bastien A, List JF. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomized, double-blind, placebo-controlled trial. Lancet. 2010;375:2223–33.CrossRefPubMed
7.
Vasilakou D, Karagiannis T, Athanasiadou E, et al. Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med. 2013;159:262–74.CrossRefPubMed
8.
Handelsman Y, Bloomgarden ZT, Grunberger G, et al. American Association of Clinical Endocrinologists and American College of Endocrinology—clinical practice guidelines for developing a diabetes mellitus comprehensive care plan—2015. Endocr Pract. 2015;21:1–87.CrossRefPubMedPubMedCentral
9.
Hardy E, Salsali A, Hruba V, et al. Efficacy increases with increasing baseline HbA1c category with dapagliflozin therapy. Diabetes. 2012;61:23.CrossRef
10.
Bailey CJ, Morales Villegas EC, Woo V, Tang W, Ptaszynska A, List JF. Efficacy and safety of dapagliflozin monotherapy in people with type 2 diabetes: a randomized double-blind placebo-controlled 102-week trial. Diabet Med. 2015;32:531–41.CrossRefPubMed
11.
Häring HU, Merker L, Seewaldt-Becker E, et al. Empagliflozin as add-on to metformin plus sulfonylurea in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial. Diabetes Care. 2013;36:3396–404.CrossRefPubMedPubMedCentral
12.
Baker WL, Smyth LR, Riche DM, Bourret EM, Chamberlin KW, White WB. Effects of sodium-glucose co-transporter 2 inhibitors on blood pressure: a systematic review and meta-analysis. J Am Soc Hypertens. 2014;8(262–75):e9.
13.
Zinman B, Lachin JM, Inzucchi SE. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2016;374:1094.CrossRefPubMed
14.
Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375:323–34.CrossRefPubMed
15.
Rossenwasser RF, Sultan S, Sutton D, Choksi R, Epstein BJ. SGLT-2 inhibitors and their potential in the treatment of diabetes. Diabetes Metab Syndr Obes. 2013;6:453–67.
16.
Hattersley AT, Thorens B. Type 2 diabetes, SGLT2 inhibitors, and glucose secretion. N Engl J Med. 2015;373:974–6.CrossRefPubMed
17.
Strojek K, Yoon KH, Hruba V, Elze M, Langkilde AM, Parikh S. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with glimepiride: a randomized, 24-week, double-blind, placebo-controlled trial. Diabetes Obes Metab. 2011;13:928–38.CrossRefPubMed
18.
Schernthaner G, Gross JL, Rosenstock J, et al. Canagliflozin compared with sitagliptin for patients with type 2 diabetes who do not have adequate glycemic control with metformin plus sulfonylurea: a 52-week randomized trial. Diabetes Care. 2013;36:2508–15.CrossRefPubMedPubMedCentral
19.
Matthaei S, Bowering K, Rohwedder K, Grohl A, Parikh S. Dapagliflozin improves glycemic control and reduces body weight as add-on therapy to metformin plus sulfonylurea: a 24-week randomized, double-blind clinical trial. Diabetes Care. 2015;38:365–72.CrossRefPubMed
20.
Wilding JP, Norwood P, T’joen C, Bastien A, List JF, Fiedorek FT. A study of dapagliflozin in patients with type 2 diabetes receiving high doses of insulin plus insulin sensitizers: applicability of a novel insulin-independent treatment. Diabetes Care. 2009;32:1656–62.CrossRefPubMedPubMedCentral
21.
Wilding JP, Woo V, Soler NG, Sugg J, Rohwedder K, Parikh S. Long-term efficacy of dapagliflozin in patients with type 2 diabetes mellitus receiving high doses of insulin: a randomized trial. Ann Intern Med. 2012;156:405–15.CrossRefPubMed
22.
Rosenstock J, Jelaska A, Zeller C, Kim G, Broedl UC, Woerle HJ. Impact of empagliflozin added on to basal insulin in type 2 diabetes inadequately controlled on basal insulin: a 78-week randomized, double-blind, placebo-controlled trial. Diabetes Obes Metab. 2015;17:936–48.CrossRefPubMedPubMedCentral
23.
Neal B, Perkovic V, De Zeeuw D, et al. Efficacy and safety of canagliflozin, an inhibitor of sodium-glucose cotransporter 2, when used in conjunction with insulin therapy in patients with type 2 diabetes. Diabetes Care. 2015;38:403–11.CrossRefPubMed
24.
Weir MR, Januszewicz A, Gilbert RE, et al. Effect of canagliflozin on blood pressure and adverse events related to osmotic diuresis and reduced intravascular volume in patients with type 2 diabetes mellitus. Diabetes Care. 2015;38:1687–93.CrossRef
25.
Peters AL, Buschur EO, Buse JB, Cohan P, Diner JC, Hirsch IB. Euglycemic diabetic ketoacidosis: a potential complication of treatment with sodium-glucose cotransporter 2 inhibition
26.
US Food and Drug Administration. FDA Drug Safety Communication: FDA warns that SGLT2 inhibitors for diabetes may result in a serious condition of too much acid in the blood (05/15/2015). http://​www.​fda.​gov/​Drugs/​DrugSafety/​ucm446845.​htm. Accessed March 2017.
27.
European Medicines Agency. Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC). SGLT2 inhibitors: recommendations to minimise risk of diabetic ketoacidosis (8-11/02/2016). http://​www.​ema.​europa.​eu/​ema/​index.​jsp?​curl=​pages/​medicines/​human/​referrals/​SGLT2_​inhibitors/​human_​referral_​prac_​000052.​jsp&​mid=​WC0b01ac05805c51​6f. Accessed March 2017.
28.
Handelsman Y, Henry RR, Bloomgarden ZT, et al. American Association of Clinical Endocrinologists and American College of Endocrinology position statement on the association of SGLT-2 inhibitors and diabetic ketoacidosis. Endocr Pract. 2016;22:753–62.CrossRefPubMed
29.
Shubrook JH, Bokaie BB, Adkins SE. Empagliflozin in the treatment of type 2 diabetes: evidence to date. Drug Des Devel Ther. 2015;9:5793–803.CrossRefPubMedPubMedCentral
30.
Liakos A, Karagiannis T, Athanasiadou E, et al. Efficacy and safety of empagliflozin for type 2 diabetes: a systematic review and meta-analysis. Diabetes Obes Metab. 2014;16:984–93.CrossRefPubMed
31.
Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009;32:193–203.CrossRefPubMedPubMedCentral
32.
Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis. JAMA. 2007;298:194–206.CrossRefPubMed
33.
Flórez H, Luo J, Castle-Florez Mitsi G, et al. Impact of metformin-induced gastrointestinal symptoms on quality of life and adherence in patients with type 2 diabetes. Postgrad Med. 2010;122:112–20.CrossRefPubMed
34.
Htike ZZ, Zaccardi F, Papamargaritis D, Webb DR, Khunti K, Davies MJ. Efficacy and safety of glucagon-like peptide-1 receptor agonists in type 2 diabetes: a systematic review and mixed-treatment comparison analysis. Diabetes Obes Metab. 2017;19:524–36.
35.
Taylor SI, Blau JE, Rother KI. Possible adverse effects of SGLT2 inhibitors on bone. Lancet Diabetes Endocrinol. 2015;3:8–10.CrossRefPubMed
36.
US Food and Drug Administration. FDA Drug Safety Communication: FDA revises label of diabetes drug canagliflozin (Invokana, Invokamet) to include updates on bone fracture risk and new information on decreased bone mineral density. 2015. http://​www.​fda.​gov/​Drugs/​DrugSafety/​ucm461449.​htm. Accessed March 2017.
37.
38.
Tang HL, Li DD, Zhang JJ, et al. Lack of evidence for a harmful effect of sodium-glucose co-transporter 2 (SGLT2) inhibitors on fracture risk among T2DM patients: a network and cumulative meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2016;18:1199–206.CrossRefPubMed
39.
Watts NB, Bilezikian JP, Usiskin K, et al. Effects of canagliflozin on fracture risk in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2016;101:157–66.CrossRefPubMed
40.
European Medicines Agency. SGLT2 inhibitors: information on potential risk of toe amputation to be included in prescribing information. http://​www.​ema.​europa.​eu/​docs/​en_​GB/​document_​library/​Press_​release/​2017/​02/​WC500222191.​pdf. Accessed March 2017.
41.
US Food and Drug Adminstration. FDA Drug Safety Communication: interim clinical trial results find increased risk of leg and foot amputations, mostly affecting the toes, with the diabetes medicine canagliflozin (Invokana, Invokamet); FDA to investigate. https://​www.​fda.​gov/​Drugs/​DrugSafety/​ucm500965.​htm. Accessed 11 March 2017.
42.
43.

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