Long‐term cisapride treatment improves diabetic gastroparesis but not glycaemic control

Abstract

Background: In patients with diabetic gastroparesis, delayed food delivery to the intestine may become a major obstacle to post‐prandial glycaemic control. Aim: To investigate whether cisapride accelerates gastric emptying in the long term or improves diabetes control in patients with diabetic gastroparesis. Methods: Eighty‐five patients with long‐standing insulin‐dependent diabetes mellitus (glycosylated haemoglobin (HbA1c) > 7.0%), dyspepsia and diabetic neuropathy were tested for impaired gastric emptying of solids by the 13C‐octanoate breath test. Nineteen of these patients with severe diabetic gastroparesis (i.e. t1/2 > 170 min) were randomly treated with 10 mg cisapride t.d.s. (n=9) or placebo (n=10) for 12 months. Thereafter, the breath test, dyspeptic symptoms and HbA1c values were reassessed. Results: Half emptying times in nine patients with diabetic gastroparesis were significantly shortened by cisapride (175 ± 46 min vs. 227 ± 40 min; P < 0.03). Half emptying times in the 10 patients taking placebo did not change (205 ± 37 min vs. 211 ± 36 min, P=0.54). Cisapride significantly reduced dyspepsia (score: 4.1 ± 1.6 vs. 2.0 ± 0.5, P=0.002). HbA1c values after 12 months of treatment were not different (cisapride: 7.7 ± 0.4% vs. 7.6 ± 0.9%, P=0.76; placebo: 7.5 ± 0.6% vs. 7.6 ± 1.5%, P=0.89). Conclusions: Prokinetic treatment with cisapride accelerates gastric emptying of solids and improves dyspeptic symptoms in diabetic gastroparesis. Glycaemic control, however, is not affected by cisapride.

Effect of the motilin agonist KC 11458 on gastric emptying in diabetic gastroparesis

“…Hence, with gastroparesis may require a higher dose is unlikely, 30 but cannot be totally excluded. While the number of subjects we included was comparable with previous studies by ourselves 6,8 and others 3,5,10 which have evaluated the effects of prokinetic drugs on gastric emptying in patients with diabetic gastroparesis with a positive outcome, a Type 2 error cannot be excluded. We are unaware of any published information about the comparative efficacy of KC 11458 and other motilin agonists, such as ABT-229 20 , in humans.…”

“…1,2 Treatment with prokinetic agents, including cisapride, domperidone, metoclopramide and erythromycin, forms the mainstay of therapy of symptomatic diabetic gastroparesis. [3][4][5][6][7][8][9][10] Short-term administration of all of these drugs has been shown to accelerate gastric emptying, although there is only a poor correlation between the magnitude of symptomatic improvement and the change in gastric emptying. [2][3][4] All of the currently available drugs have significant limitations.…”

“…[2][3][4] All of the currently available drugs have significant limitations. 4 Until recently, cisapride was arguably the drug of first choice, 6,10 but the recent recognition of adverse cardiac effects have led to substantial restrictions in its use. 11 It has also been demonstrated that the gastrokinetic effect of at least some of these drugs (including erythromycin and cisapride) is attenuated during hyperglycaemia; [12][13][14][15][16][17][18] the latter is known to slow gastric emptying in patients with diabetes, as well as healthy subjects.…”

Prevalence and determinants of delayed gastric emptying in hospitalised Type 2 diabetic patients

“…This is likely to confound a potential association with the duration of diabetes. In the past autonomic neuropathy was considered to be the main factor causing gastroparesis, but it is clear that any relationship between gastric emptying and cardiovascular autonomic function is weak [5,12,33] . The prevalence of autonomic nerve dysfunction observed in this study is higher than that reported in groups with a similar duration of diabetes (about 65% after 10 years) [34] what is likely to reflect the methodology used.…”

“…In Type 1 patients it is recognised that the rate of gastric emptying is modulated by acute changes in blood glucose concentration (gastric emptying is slower during hyperglycemia [8,9] and accelerated during hypoglycemia [10] ) and autonomic nerve function. The relationship between gastroparesis and autonomic dysfunction is, however, relatively weak [11,12] . The prevalence of gastroparesis is also dependent on the duration of diabetes and may be higher in females than males [13] .…”