Imeglimin population pharmacokinetics and dose adjustment predictions for renal impairment in Japanese and Western patients with type 2 diabetes

Bariatric surgery is a known and effective treatment for type 2 diabetes mellitus. Patients with type 1 diabetes mellitus and exogenous insulin-requiring type 2 diabetes mellitus require adjusted insulin dosing after surgery to avoid hypoglycemia. This review describes insulin dose adjustments following a variety of bariatric procedures. After searching the available literature and assessing for eligibility, 8 articles were included. The Johns Hopkins Research Evidence Appraisal Tool for literature appraisal was used. The results of this review reveal insulin dose adjustment varies based upon surgical procedure type and time of follow-up from the procedure.

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Long-term efficacy and safety of oral semaglutide and the effect of switching from sitagliptin to oral semaglutide in patients with type 2 diabetes: a 52-week, randomized, open-label extension of the PIONEER 7 trial

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001649 ◽

2020 ◽

Vol 8 (2) ◽

pp. e001649

Author(s):

John B Buse ◽

Bruce W Bode ◽

Ann Mertens ◽

Young Min Cho ◽

Erik Christiansen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Body Weight ◽

Dose Adjustment ◽

Main Phase ◽

Open Label ◽

Open Label Extension ◽

Registration Number ◽

Flexible Dose

IntroductionThe PIONEER 7 trial demonstrated superior glycemic control and weight loss with once-daily oral semaglutide with flexible dose adjustment versus sitagliptin 100 mg in type 2 diabetes. This 52-week extension evaluated long-term oral semaglutide treatment and switching from sitagliptin to oral semaglutide.Research design and methodsA 52-week, open-label extension commenced after the 52-week main phase. Patients on oral semaglutide in the main phase continued treatment (n=184; durability part); those on sitagliptin were rerandomized to continued sitagliptin (n=98) or oral semaglutide (n=100; initiated at 3 mg) (switch part). Oral semaglutide was dose-adjusted (3, 7, or 14 mg) every 8 weeks based on glycated hemoglobin (HbA1c) (target <7.0% (<53 mmol/mol)) and tolerability. Secondary endpoints (no primary) included changes in HbA1c and body weight.ResultsIn the durability part, mean (SD) changes in HbA1c and body weight from week 0 were –1.5% (0.8) and –1.3% (1.0) and –2.8 kg (3.8) and –3.7 kg (5.2) at weeks 52 and 104, respectively. In the switch part, mean changes in HbA1c from week 52 to week 104 were –0.2% for oral semaglutide and 0.1% for sitagliptin (difference –0.3% (95% CI –0.6 to 0.0); p=0.0791 (superiority not confirmed)). More patients achieved HbA1c <7.0% with oral semaglutide (52.6%) than sitagliptin (28.6%; p=0.0011) and fewer received rescue medication (9% vs 23.5%). Respective mean changes in body weight were –2.4 kg and –0.9 kg (difference –1.5 kg (95% CI –2.8 to –0.1); p=0.0321). Gastrointestinal adverse events were the most commonly reported with oral semaglutide.ConclusionsLong-term oral semaglutide with flexible dose adjustment maintained HbA1c reductions, with additional body weight reductions, and was well tolerated. Switching from sitagliptin to flexibly dosed oral semaglutide maintained HbA1c reductions, helped more patients achieve HbA1c targets with less use of additional glucose-lowering medication, and offers the potential for additional reductions in body weight.Trial registration numberNCT02849080.

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Management of patients with type 2 diabetes and mild/moderate renal impairment: profile of linagliptin

Therapeutics and Clinical Risk Management ◽

10.2147/tcrm.s67076 ◽

2015 ◽

pp. 799 ◽

Cited By ~ 6

Author(s):

Baptist Gallwitz

Keyword(s):

Type 2 Diabetes ◽

Renal Impairment ◽

Moderate Renal Impairment

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SP453ANKLE-BRACHIAL INDEX IS ASSOCIATED WITH RENAL IMPAIRMENT IN PATIENTS WITH ARTERIAL HYPERTENSION AND TYPE 2 DIABETES MELLITUS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfx149.sp453 ◽

2017 ◽

Vol 32 (suppl_3) ◽

pp. iii275-iii275

Author(s):

Elena Troitskaya ◽

Ekaterina Starostina ◽

Zhanna Kobalava

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Renal Impairment ◽

Arterial Hypertension

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OP60 EFFICACY AND SAFETY OF LIRAGLUTIDE VERSUS PLACEBO IN SUBJECTS WITH TYPE 2 DIABETES AND MODERATE RENAL IMPAIRMENT (LIRA-RENAL): A RANDOMISED TRIAL

Diabetes Research and Clinical Practice ◽

10.1016/s0168-8227(14)70266-9 ◽

2014 ◽

Vol 106 ◽

pp. S31 ◽

Cited By ~ 1

Author(s):

C. Mathieu ◽

G. Umpierrez ◽

S. Atkin ◽

S. Bain ◽

P. Rossing ◽

...

Keyword(s):

Type 2 Diabetes ◽

Renal Impairment ◽

Randomised Trial ◽

Moderate Renal Impairment ◽

Efficacy And Safety

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Abstract 11267: LX4211, a Dual Inhibitor of Sodium-Glucose Cotransporters 1 and 2, Reduces Systolic Blood Pressure in Patients With Type 2 Diabetes Mellitus and Moderate to Severe Renal Impairment

Circulation ◽

10.1161/circ.130.suppl_2.11267 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Pablo Lapuerta ◽

Paul Strumph ◽

Philip Banks ◽

Ikenna Ogbaa ◽

Brian Zambrowicz ◽

...

Keyword(s):

Diabetes Mellitus ◽

Blood Pressure ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Renal Impairment ◽

Systolic Blood Pressure ◽

Severe Renal Impairment ◽

Postprandial Glucose ◽

Dual Inhibitor

Introduction: Selective sodium-glucose cotransporter 2 (SGLT2) inhibitors target only the kidney, and they have reduced efficacy when patients with type 2 diabetes mellitus (T2DM) have renal impairment (RI). LX4211 blocks sodium and glucose absorption in the gastrointestinal tract by inhibition of SGLT1, and it enhances urinary sodium and glucose excretion in the urine through inhibition of SGLT2. The dual SGLT1/2 action of LX4211 was anticipated to reduce systolic blood pressure (SBP) in addition to improving glucose control in the setting of RI. Methods: This analysis explored the effect of LX4211 on SBP in a clinical trial of patients with T2DM and moderate to severe RI. Patients (N=31) were randomly assigned to be treated with LX4211 (400 mg, N=16) or placebo (N=15) qd for 7 consecutive days. Postprandial glucose levels after a standard high glucose meal served as the primary measure of pharmacodynamic activity. Baseline and Day 8 trough SBP measures were each an average of 3 seated assessments. Results: Mean baseline characteristics included age 66.4 years, estimated glomerular filtration rate (eGFR) 43.4 mL/min/1.73 m 2 , and SBP 130.9 mmHg. Postprandial glucose area under the curve (sampled from pre-dose to 4 hours post meal) was reduced from Baseline to Day 7 by 169.3 mg*hr/dL on LX4211 compared to placebo (p=0.003). Day 8 SBP reductions were 11.4 mmHg on LX4211 and 0.0 mmHg on placebo (p=0.045 for difference between groups). Patients with greater RI (eGFR <45 mL/min/1.73 m2) treated with LX4211 (N=6) had a 10.5 mmHg SBP reduction compared to 0.3 mmHg on placebo (N=9). The difference between seated and standing SBP did not change with LX4211 (0.0 mmHg change, Day 8 vs. Baseline). There were no reports of hypotension, hypovolemia, no serious adverse events, and no patient discontinued due to an adverse event. Mild hypoglycemia was reported in 1 LX4211 patient compared to 2 placebo patients. Conclusions: LX4211 may reduce SBP and enhance glycemic control in T2DM patients with moderate to severe RI.

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