Combination Therapy With Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors in Older Patients With Type 2 Diabetes: A Real-World Evidence Study

Gómez, Juana Carretero; Arévalo-Lorido, José Carlos; Huelgas, Ricardo Gómez; Lucas, Dolores García de; Polo, Lourdes Mateos; Aguilar, José Manuel Varela; Ripoll, José Miguel Seguí; Ena, Javier; Diabetes, Obesity

doi:10.1016/j.jcjd.2018.09.001

Cited by 18 publications

(8 citation statements)

References 29 publications

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“…The same safety profile has also been observed in other randomised trials, with drug discontinuation rates because of severe side effects of less than 3% 6,25 . We have also confirmed the safety of GLP‐1ra and SGLT2i in a real‐world study that includes elderly patients 28 …”

Section: Discussionsupporting

confidence: 86%

Early biomarkers of diabetic kidney disease. A focus on albuminuria and a new combination of antidiabetic agents

Gómez¹,

Ena

Ripoll

et al. 2020

Int. J. Clin. Pract.

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Aims We aimed to determine the efficacy and safety of sodium‐glucose cotransporter type 2 inhibitors (SGLT2i) and glucagon‐like peptide‐1 receptor agonists to prevent worsening urinary albumin‐to‐creatinine ratio as an early biomarker of diabetes kidney disease. Methods A total of 178 patients with type 2 diabetes and obesity received combination treatment with SGLT2i added to GLP1ra (n = 76), GLP1ra added to SGLT2i (n = 50) or GLP1ra plus SGLT2i from start (n = 52), according to investigators´ best clinical judgement. Major outcomes assessed at 26 weeks were changes in urine albumintocreatinine‐ratio (UACR), estimated glomerular filtration rate (eGFR), glycated haemoglobin, body weight and systolic blood pressure. Results All patients (58.6% men, mean age 61.9 ± 10.0 years) completed the study. Baseline HbA1c, weight and eGFR levels were 8.2 ± 0.9%, 109.9 ± 19 kg and 83.3 ± 19.6 mL/min/m2, respectively. At 26 weeks, we found significant reductions in HbA1c (1.16%), weight (5.17 kg) and systolic blood pressure (8.13 mmHg). The reduction in UACR was 15.14 mg/g (95% CI 8.50‐22.4) (−24.6 ± 64.7%), which was greatest in the group of patients with SGLT2i added on to GLP1ra therapy (116.7 mg/g; 95% CI: 54‐296.5 mg/g; P < .001. Patients with urinary albumin‐to‐creatinine ratio ≥30 mg/g, showed a higher declines (63.18 mg/g [95% CI 44.5‐104.99]) (−56 ± 65.9%). The greatest reduction in urinary albumin‐to‐creatinine ratio was obtained when SGLT2i was added to GLP1ra (116.7 mg/g). The eGFR did not significantly change along the study period. Conclusion Our results show the beneficial effect of GLP1ra and SGLT2i combination therapy on early biomarkers of diabetes kidney disease such as albuminuria and in other significant outcomes for diabetes control.

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Section: Discussionsupporting

confidence: 86%

Early biomarkers of diabetic kidney disease. A focus on albuminuria and a new combination of antidiabetic agents

Gómez¹,

Ena

Ripoll

et al. 2020

Int. J. Clin. Pract.

Self Cite

View full text Add to dashboard Cite

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“…There are two methods for initiating combination therapy-sequential initiation and simultaneous initiation. Comparing both methods, simultaneous initiation led to a greater and more rapid reduction in HbA1c and weight, although these differences were unlikely to be significant in the long term [13,14]. The American Diabetes Association (ADA) recommends the sequential initiation of GLP-1 agonist and/or SGLT2 inhibitor in four groups of patients: established atherosclerotic cardiovascular disease, heart failure or chronic kidney disease, obesity and at risk of hypoglycemia.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, it is likely that sequential initiation would be the more commonly adopted approach, including Patient #1 in whom liraglutide was started followed by SGLT2 inhibitor, and Patient #2 in whom liraglutide was added to existing SGLT2 inhibitor therapy. Gomez et al [15] found that a greater reduction in HbA1c and weight was observed when GLP-1 agonist was added to existing treatment with an SGLT2 inhibitor, rather than vice versa [13]-which was the approach in Patient #2.…”

Section: Discussionmentioning

confidence: 99%

High-Dose Liraglutide and SGLT2 Inhibitor: A Promising Combination

Chua

2021

Clinics and Practice

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Sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) agonists are important drugs in our armamentarium of treatment for Type 2 diabetes mellitus (DM). In addition to their glucose-lowering effects, they have effects on weight, other metabolic diseases and perhaps most importantly, a cardioprotective and reno-protective effect. Liraglutide is a long-acting GLP-1 agonist which was originally used at 1.8 mg daily for the treatment of DM. However, high-dose liraglutide—liraglutide 3 mg daily, has been demonstrated to be a safe and effective treatment for obesity, with or without DM. In this manuscript, I present two patients who had unusual responses to combination therapy with high-dose liraglutide and SGLT2 inhibitor—marked and/or rapid improvement in glycemic control and weight loss. Drawing from the observations in both cases, I discuss the complementary mechanisms of actions of both drugs, review the clinical effects of combination therapy and distil them into clinical pearls of practical utility for the physician. Given the “clash of the two pandemics” of obesity and COVID-19 and the burgeoning rates of obesity which loom in the near horizon, this is most timely.

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“…Moreover, real‐world evidence of efficacy and safety has been collected in a group of elderly patients with T2DM who had suboptimal glycemic control. 30 Most recent trials of SGLT2 inhibitors for efficacy of reduction in heart failure incidence or renal outcome have enrolled not only diabetic patients but also non‐diabetic patients. 31 , 32 In those studies, there was no significant difference in safety between diabetic and non‐diabetic patients.…”

Section: Discussionmentioning

confidence: 99%

Safety and efficacy of empagliflozin in elderly Japanese patients with type 2 diabetes mellitus: A post hoc analysis of data from the SACRA study

Okada

Hoshide

Kato³

et al. 2020

J of Clinical Hypertension

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Elderly diabetic patients are likely to have uncontrolled nocturnal hypertension, which confers higher risks of cardiovascular events and heart failure. To investigate the efficacy and safety of empagliflozin in elderly patients with type 2 diabetes (T2DM), a sub‐analysis was performed of data from the SGLT2 inhibitor and Angiotensin receptor blocker Combination theRapy in pAtients with diabetes and uncontrolled nocturnal hypertension (SACRA) study, a multi‐center, double‐blind, randomized, parallel study of T2DM patients who were treated with empagliflozin for 12 weeks. In the present analysis, we compared efficacy and safety outcomes in participants aged <75 and ≥75 years. At baseline, 44 participants were ≥75 years and 87 were <75 years. Nighttime ambulatory systolic blood pressure (SBP) decreased by 4.2 mm Hg in the ≥75‐year‐old group and by 7.9 mm Hg in the <75‐year‐old group (p = .884 for the between‐age group difference in the change between baseline and week 12) [primary endpoint]. Empagliflozin, but not placebo, significantly reduced mean 24‐h SBP (−8.7 mm Hg in ≥75‐year‐olds vs. −11.0 mm Hg in <75‐year‐olds) and daytime SBP (−10.8 mm Hg in ≥ 75‐year‐olds vs. −12.3 mm Hg in <75‐year‐olds) between baseline and week 12, with no significant differences between the groups. In addition, there were significant reductions in glycated hemoglobin, body weight, and uric acid during 12 weeks of empagliflozin treatment in the two age groups. The incidences of hypoglycemic episodes, hypotension, and metabolic adverse events were similar in the two groups. Thus, empagliflozin was effective and well tolerated in elderly diabetic patients with uncontrolled nocturnal hypertension when administered for 12 weeks.

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Combination Therapy With Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors in Older Patients With Type 2 Diabetes: A Real-World Evidence Study

Cited by 18 publications

References 29 publications

Early biomarkers of diabetic kidney disease. A focus on albuminuria and a new combination of antidiabetic agents

Early biomarkers of diabetic kidney disease. A focus on albuminuria and a new combination of antidiabetic agents

High-Dose Liraglutide and SGLT2 Inhibitor: A Promising Combination

Safety and efficacy of empagliflozin in elderly Japanese patients with type 2 diabetes mellitus: A post hoc analysis of data from the SACRA study

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