Frequency Of Gastrointestinal Adverse Events Research Articles

Evaluation of the frequency of gastrointestinal adverse events associated with the use of prolonged-release metformin hydrochloride

Diabetes mellitus is defined by hyperglycemia resulting from impaired insulin action or distress, or both. Metformin is widely prescribed to control the disease and the most common adverse events caused by its use are diarrhea, nausea and/or abdominal discomfort. We evaluated the frequency profile of gastrointestinal adverse events associated with the use of metformin. This is a cross-sectional observational study, in which the occurrence of diarrhea in patients with type 2 diabetes mellitus who started treatment with metformin hydrochloride at a dose of 500 mg of prolonged release was reported. 12 (41.37%) participants were male and 17 (58.62%) were female. Diarrhea was present (n=16) in more than half of the patients (55.2%) who used the drug. Patients had an average of 12 episodes of diarrhea per month. There was also the presence of abdominal discomfort (n=7), in which 24.1% reported being very high. The study showed that the extended-release drug metformin hydrochloride 500 mg can cause gastrointestinal adverse events at the start of treatment and lasts for approximately twelve days.

Nasal Delivery of Acute Medications for Migraine: The Upper Versus Lower Nasal Space.

The acute treatment of migraine requires effective drugs that are well tolerated and provide rapid and consistent pain relief. Oral tablets are the most commonly used acute treatment for migraine; however, their effectiveness is limited by the rate of gastrointestinal (GI) tract absorption and first-pass hepatic metabolism, and they may not be ideal for patients experiencing GI motility issues. Nasal delivery is an attractive alternative route as it may circumvent GI tract absorption, avoid first-pass metabolism in the liver, and potentially reduce the frequency of GI adverse events. The large surface area and high vascularity within the nose may permit rapid absorption of therapeutics into the systemic circulation, allowing for rapid onset of action. However, the site of drug deposition (upper versus lower nasal cavity) may influence drug pharmacokinetics. Most approved nasal migraine therapies target the lower nasal space where the epithelium is less permeable, and they may be quickly cleared away due to increased ciliary function or dripping from the nose or swallowing, resulting in variable absorption and limited bioavailability. Together with its abundant vascularization, relative mucosal thickness stability, and low clearance rates, the upper nasal space harnesses the benefits of nasal delivery to potentially maximize drug efficacy.

637-P: Effectiveness of Fixed Ratio Combination of IGlarLixi in People with Type 2 Diabetes Mellitus: Experience from Routine Clinical Practice

Background: Currently no data are available on the real-world effectiveness of the fixed ratio combination of insulin glargine 100 U/ml and lixisenatide (iGlarLixi). This non-interventional study (it was conducted in Hungary) aimed to evaluate its effects on glycaemic control and hypoglycaemia in real-world practice. Methods: The single-arm, 6-month (with follow-up visits at 3 and 6 months) study included uncontrolled adults with type 2 diabetes (HbA1c>7,5%) treated by oral antidiabetics (OAD) +/- basal insulin. iGlarLixi treatment was started at the time of inclusion. Results: Of the included 442 participants, 353 were involved in the efficacy analyses. 282 (79.9%) subjects were treated with OADs, while the remaining 71 (20.1%) with basal insulin and OAD(s) before inclusion. The proportion of participants achieving at least 1.0% HbA1c reduction during the observation period was 60.9% (primary endpoint). All glycaemic variables (mean±SD) improved significantly (p<0,001) during follow-up (HbA1c from 8.9±1.3% to 7.4 ±1.0%, fasting blood glucose from 9.0±2.2 mmol/L to 6.9±1.2 mmol/L, and postprandial blood glucose from 11.3±2.3 mmol/L to 8.5±1.5 mmol/L). All changes were clinically and statistically significant. Body weight was also decreased from 90.5±18.0 kg to 88.2±17.8 kg. Only 37 subjects (10.5%) self-reported at least one symptomatic hypoglycaemic episode during the study. There was no severe hypoglycaemic episode being reported. Frequency of gastrointestinal adverse events was low (5 patients, 1.4%). Conclusion: The first prospective, non-interventional study confirmed several results from the LIXILAN programme in a real-life setting. iGlarLixi significantly improved glycaemic control with low frequency of hypoglycaemia and gastrointestinal adverse events in a heterogenous population of people with type 2 diabetes. Results confirm similar efficacy and safety in routine clinical care than in randomized controlled trials. Disclosure J. T. Kis: None. G. Nagy: Employee; Self; Sanofi-Aventis. P. Stella: Employee; Self; Sanofi-Aventis. Funding Sanofi

CT imaging findings of lenvatinib-induced enteritis.

To evaluate the relationship between abnormal findings on abdomino-pelvic CT and adverse events in oncologic patients treated with lenvatinib, and their relationship with treatment planning. This single institutional retrospective study included 58 patients with unresectable hepatocellular carcinoma or unresectable thyroid carcinoma (mean age ± standard deviation 69.6 ± 10.0years; range 39-84years; 48 men) who underwent CT between October 2016 and July 2020. Two radiologists who were blinded to clinical information including the presence or absence ofdiarrhea evaluated the imaging findings, including the presence/absence of enteritis in each intestinal segment. Gastrointestinal adverse events (diarrhea, decreased appetite, nausea, and vomiting) and other drug-induced adverse events requiring treatment or follow-up during lenvatinib treatment were also investigated. The frequency of these adverse events was compared between the patients with and without enteritis using Fisher's exact test or the Mann-Whitney U test. Enteritis was found on CT in the majority (33/58 [56.9%]) of the patients, and most of them (25/33 [75.8%]) showed duodenojejunitis. The frequency of gastrointestinal adverse events (28/33 [84.8%] vs. 13/25 [56.0%], p = 0.009), diarrhea (20/33 [60.6%] vs. 3/25 [12.0%], p < 0.001), and drug interruptions (25/33 [75.8%] vs. 10/25 [40.0%], p = 0.008) and the number of other adverse events (3.9 ± 1.7 vs. 2.3 ± 1.3, p < 0.001) were significantly higher in the patients with enteritis on CT than in those without. Lenvatinib-induced enteritis frequently involved the duodenum and jejunum and was related to a significantly higher frequency of treatment interruptions and gastrointestinal adverse events.

Diroximel fumarate in the treatment of multiple sclerosis.

Diroximel fumarate (DRF) is a new emerging therapy for patients with multiple sclerosis. The levels of its active metabolite, monomethyl fumarate, are bioequivalent to the levels generated from dimethyl fumarate (DMF) treatment. The efficacy and safety profiles of DRF are expected to be similar to the well-established profiles of DMF. The metabolism of DRF leads to lower concentration of methanol in the small intestine than with DMF and thus reduced severity and frequency of gastrointestinal adverse events. DRF seems a promising alternative to DMF and other first-line therapies for multiple sclerosis. The current review is based on the two existing Phase III trials of DRF: the interim analysis of the EVOLVE-MS-1 trial and the completed EVOLVE-MS-2 trial.

Liraglutide in Children and Adolescents with Type 2 Diabetes

BackgroundMetformin is the regulatory-approved treatment of choice for most youth with type 2 diabetes early in the disease. However, early loss of glycemic control has been observed with metformin monotherapy. Whether liraglutide added to metformin (with or without basal insulin treatment) is safe and effective in youth with type 2 diabetes is unknown.MethodsPatients who were 10 to less than 17 years of age were randomly assigned, in a 1:1 ratio, to receive subcutaneous liraglutide (up to 1.8 mg per day) or placebo for a 26-week double-blind period, followed by a 26-week open-label extension period. Inclusion criteria were a body-mass index greater than the 85th percentile and a glycated hemoglobin level between 7.0 and 11.0% if the patients were being treated with diet and exercise alone or between 6.5 and 11.0% if they were being treated with metformin (with or without insulin). All the patients received metformin during the trial. The primary end point was the change from baseline in the glycated hemoglobin level after 26 weeks. Secondary end points included the change in fasting plasma glucose level. Safety was assessed throughout the course of the trial.ResultsOf 135 patients who underwent randomization, 134 received at least one dose of liraglutide (66 patients) or placebo (68 patients). Demographic characteristics were similar in the two groups (mean age, 14.6 years). At the 26-week analysis of the primary efficacy end point, the mean glycated hemoglobin level had decreased by 0.64 percentage points with liraglutide and increased by 0.42 percentage points with placebo, for an estimated treatment difference of −1.06 percentage points (P<0.001); the difference increased to −1.30 percentage points by 52 weeks. The fasting plasma glucose level had decreased at both time points in the liraglutide group but had increased in the placebo group. The number of patients who reported adverse events was similar in the two groups (56 [84.8%] with liraglutide and 55 [80.9%] with placebo), but the overall rates of adverse events and gastrointestinal adverse events were higher with liraglutide.ConclusionsIn children and adolescents with type 2 diabetes, liraglutide, at a dose of up to 1.8 mg per day (added to metformin, with or without basal insulin), was efficacious in improving glycemic control over 52 weeks. This efficacy came at the cost of an increased frequency of gastrointestinal adverse events. (Funded by Novo Nordisk; Ellipse ClinicalTrials.gov number, NCT01541215.)

ASCEND-8 pharmacokinetic, safety, and efficacy data for ceritinib 450 mg with food in patients with anaplastic lymphoma kinase–positive non-small cell lung Cancer: A clinical perspective

Anaplastic lymphoma kinase–positive (ALK+) non-small cell lung cancer (NSCLC) is diagnosed in up to 126,000 patients worldwide annually. Ceritinib is a next-generation ALK-targeted tyrosine kinase inhibitor that is approved for the treatment of patients with metastatic ALK+ NSCLC. In December 2017, the US Food and Drug Administration–approved dose of ceritinib was changed from 750 mg/day under fasting conditions to 450 mg/day taken with food for the treatment of patients with ALK+ NSCLC. This change was implemented on the basis of data from studies designed to investigate ways to reduce the frequency of gastrointestinal adverse events noted in patients enrolled in several ASCEND clinical trials that evaluated a ceritinib 750-mg fasted dose as either first- or second/third-line treatment. This review highlights and discusses published findings from the ASCEND-8 food-effect trial and includes commentary from physicians regarding their own clinical cases of patients who were enrolled in the trial and treated with either the 750-mg fasted or 450-mg fed dose of ceritinib. The review also discusses the implications of using the recently approved ceritinib 450-mg dose in the clinical setting.

Use of glucagon-like peptide-1 receptor agonists among individuals on basal insulin requiring treatment intensification.

As Type 2 diabetes progresses, treatment is intensified with additional therapies in an effort to manage hyperglycaemia effectively and therefore avoid complications. When greater efficacy is required, options for injectable treatments include glucagon‐like peptide‐1 receptor agonists and insulin, which may be added on to oral glucose‐lowering treatments. Among individuals receiving long‐acting basal insulin as their first injectable treatment, ~40−60% are unable to achieve or maintain their target HbA1c goals. For these people, treatment intensification options are relatively limited and include the addition of short‐acting prandial insulin or a glucagon‐like peptide‐1 receptor agonist. Glucagon‐like peptide‐1 receptor agonists vary in their effects, with short‐ and long‐acting agents having a greater impact on postprandial and fasting hyperglycaemia, respectively. Studies comparing treatment intensification options have found both glucagon‐like peptide‐1 receptor agonists and prandial insulin to be effective in reducing HbA1c concentrations; however, recipients of glucagon‐like peptide‐1 receptor agonists lost weight and had a greater frequency of gastrointestinal adverse events, whereas those receiving prandial insulin gained weight and had a greater incidence of hypoglycaemia. In addition to the separate administration of a glucagon‐like peptide‐1 receptor agonist and basal insulin, fixed‐ratio combinations of a glucagon‐like peptide‐1 receptor agonist and basal insulin offer a single administration for both treatments but have less flexibility in dose titration than treatment with their individual components. For individuals who require treatment intensification beyond basal insulin, use of these various options allows physicians to target the individual needs of their patients for the achievement of optimal long‐term glycaemic control.

Etelcalcetide for the treatment of secondary hyperparathyroidism

ABSTRACTIntroduction: Calcium sensing receptor is an important target for the treatment of secondary hyperparathyroidism (SHPT). Etelcalcetide hydrochloride is a novel peptide calcimimetic agent that has a similar mechanism of action as cinacalcet hydrochloride. Clinical trials of etelcalcetide have been performed in the US, Europe, and Japan, and these trials demonstrated the safety and efficacy of etelcalcetide in dialysis patients. Etelcalcetide has recently been approved in Europe, the US and Japan.Areas covered: We review the development, pharmacokinetics, and clinical efficacy and safety of etelcalcetide for the treatment of SHPT in hemodialysis patients. We also summarize the clinical evidence regarding cinacalcet to forecast the potential clinical benefit of etelcalcetide.Expert opinion: Etelcalcetide is an injectable calcimimetic with a longer elimination half-life than cinacalcet. The injectable formulation improves adherence and reduces pill burden, while the frequency of gastrointestinal adverse events has been comparable between cinacalcet and etelcalcetide. The longer half-life of etelcalcetide reduces the fluctuation of biochemical markers of mineral and bone metabolism, but it remains to be determined whether such a sustained effect results in improved outcomes. Further studies are needed to determine the impact of etelcalcetide on clinical outcomes, particularly in comparison with the conventional calcimimetic cinacalcet.

Safety and efficacy of topical ketoprofen in transfersome gel in knee osteoarthritis: A systematic review.

Topical ketoprofen in Transfersome gel has been used for the alleviation of symptoms in osteoarthritis. Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with various side effects. Topical NSAIDs are known to have a lower side-effect profile when compared with systemic administration. The present systematic review aimed to determine the safety and efficacy of topical ketoprofen in Transfersome gel in knee osteoarthritis (OA). A systematic literature review was performed. The electronic databases EMBASE, MEDLINE, HealthStar and PubMed were searched from 1946 to June 2016. A screen of the reference sections of the included studies was also performed. Two blinded reviewers searched, screened, abstracted and evaluated the data quality using the Jadad scale. Studies were included if they contained: at least 50% of participants with knee OA, topical ketoprofen, human subjects and participants from North America or Europe. Study outcomes had to include patient-reported functional outcome scores. Five studies were included, with a total of 3619 participants, and a mean Jadad score of 3.4/5. Western Ontario McMaster Universities (WOMAC) Osteoarthritis Index was the only outcome measure consistent across all of the randomized controlled trials included in the present review (four of the five included studies). All topical ketoprofen in Transfersome gel groups (25mg, 50mg and 100mg) had improvements in pain that were superior to all other treatment arms, and the 50mg topical ketoprofen in Transfersome gel group had functional gains that were superior to all other treatment arms. The majority of the adverse events were non-serious and related to skin and subcutaneous tissue disorders, with erythema being the most common. The average of all adverse events and gastrointestinal (GI) adverse events was highest in the oral celecoxib group (47.1% and 15.1%, respectively). The average frequency of GI adverse events in the topical ketoprofen groups was comparable with that in the topical placebo treatment arm. A meta-analysis was not feasible due to the heterogeneity among the studies. Topical ketoprofen in Transfersome gel is an effective means of treating symptoms of knee OA, and is superior to oral celecoxib, oral placebo and topical placebo. The most commonly reported adverse events associated with the use of topical ketoprofen in Transfersome gel were non-severe skin and subcutaneous tissue disorders. Furthermore, as topical ketoprofen in Transfersome gel was associated with fewer adverse events when compared with oral celecoxib, and had rates of GI adverse events comparable with those of topical placebo, it may be ideal for those who are unable to take oral NSAIDs.

Vildagliptin: clinical trials programme in monotherapy and combination therapy for type 2 diabetes

As part of an extensive clinical development programme in patients with type 2 diabetes (T2DM), vildagliptin 50 mg once daily and twice daily, and 100 mg once daily have been assessed in placebo-controlled and, more importantly, in head-to-head active-comparator monotherapy trials over a wide range of baseline HbA1c levels and in a large number of elderly patients. Notable findings in individual trials included: comparable HbA1c lowering over 24 weeks with 100 mg once daily or 50 mg twice daily; efficacy comparable to rosiglitazone with reduced risk of weight gain and oedema over 24 weeks; and durable glycaemic control for up to 2 years with a reduced frequency of gastrointestinal adverse events compared with metformin. Pooled monotherapy data indicate that vildagliptin 100 mg daily produces consistent and clinically meaningful reductions in HbA1c across a range of initial HbA1c levels, in patients with lower and greater body mass index, and in younger and older patients. To date, the safety/tolerability profile seems comparable to placebo with neutral effects on body weight and lipid profiles, and minimal risk of hypoglycaemia. A preliminary study in subjects with impaired glucose tolerance showed that vildagliptin 50 mg once daily enhanced islet cell function, reduced glycaemic excursions and was very well tolerated, paving the way for a future trial in diabetes prevention. Vildagliptin has also been extensively studied in multiple clinical scenarios as add-on combination therapy in patients with inadequate glycaemic control on metformin, thiazolidinedione, sulfonylurea and insulin treatment, and has consistently been shown to improve glycaemic control with good tolerability and low risk for hypoglycaemia. In a trial in patients receiving metformin, the addition of vildagliptin 50 mg twice daily resulted in a 1.1% reduction in HbA1c at 24 weeks. Compared with add-on pioglitazone 30 mg daily in patients inadequately controlled with ongoing metformin therapy, vildagliptin 50 mg twice daily reduced HbA1c by 0.9% vs. 1.0% and was not associated with weight gain (+0.3 kg vs. +1.9 kg) over 24 weeks. Most notably, vildagliptin plus pioglitazone as initial combination therapy in drug-naive patients resulted in robust HbA1c reductions of 1.9% from baseline. In patients receiving stable insulin therapy, vildagliptin 50 mg twice daily improved glycaemic control and was associated with a significant reduction in hypoglycaemic episodes over 24 weeks. Vildagliptin shows considerable promise as a partner for metformin and other commonly used oral antidiabetic agents, and may well play an important role in combination with insulin therapy to further improve glycaemic control.

The Renal Effects of Traditional Nonsteroidal Anti-Inflammatory Agents Versus Cyclooxygenase-2 Inhibitors

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for the management of acute and chronic pain as well as for rheumatoid arthritis and osteoarthritis. Although gastrointestinal complications are the most common adverse events associated with the use of these drugs, the renal adverse effects such as acute renal failure, electrolyte abnormalities, nephrotic syndrome, interstitial nephritis, and papillary necrosis can be serious. The cyclooxygenase-2 (COX-2)- selective NSAIDs (celecoxib, rofecoxib) have been associated with a reduced frequency of gastrointestinal adverse events, but questions still remain as to their renal safety. Recent information has suggested an increased role for COX-2 as a constitutive renal enzyme, thus implying its importance for normal kidney homeostasis. Clinical studies and published case reports of renal adverse events associated with COX-2 inhibitors suggest that patients with decreased effective circulating blood volume, salt depletion, and renal insufficiency have an increased likelihood of renal-related adverse events. Because many older patients have conditions that place them in one of the “at-risk” categories, this population should be monitored closely for the development of renal adverse events from any NSAIDs, including COX-2-selective agents.

Atovaquone plus proguanil versus halofantrine for the treatment of imported acute uncomplicated Plasmodium falciparum malaria in non-immune adults: a randomized comparative trial.

In endemic zones, the atovaquone-proguanil (AP) combination is well tolerated and effective in treating acute, uncomplicated malaria. Trials involving non-immune patients are lacking, however. We conducted a randomized, multicenter open-label trial to determine the efficacy and tolerability of the AP combination (1,000 mg + 400 mg once daily for 3 days) in comparison with halofantrine (HF) (1,500 mg in 3 doses) in non-immune adults with imported uncomplicated Plasmodium falciparum malaria. Follow-up visits were programmed on Days 7, 14, 21, 28, and 35 after hospital discharge. Out of 48 patients enrolled in the study, 41 were assessable for the cure rate (21 in the AP group and 20 in the HF group). All the patients were cured. The mean parasite clearance time was longer (63+/-23 hours) in the AP group than in the HF group (48+/-15 hours) (P = 0.02). The frequency of gastrointestinal adverse events was higher in the AP group. No noteworthy electrocardiographic changes were observed, particularly in the QTc interval. The AP combination appears to be a valuable alternative treatment in non-immune adults.

Pharmacoepidemiology of non-steroidal anti-inflammatory drug use in Nottingham general practices.

To investigate the pharmacoepidemiology of NSAID usage in Nottingham general practices. Questionnaire sent to 1137 consecutive recipients of an NSAID prescription from 21 doctors in six general practices with computerized records. Patient responses were subsequently linked to data held on the practice records. General practices in and around Nottingham, selected to reflect local variations in number of partners, list size, geographical location, deprivation, prescribing burden and prescribing rate. Unselected patients receiving NSAIDs prescribed for all indications. Indication for treatment, differences in prescribing to different age groups, compliance and overall scheme drug exposure, drug effectiveness and tolerability, possible drug-related adverse events, patients' overall satisfaction with treatment and estimated costs of care. NSAIDs were used for a wide range of conditions and only a small number of patients had rheumatoid arthritis. The main drugs used were ibuprofen, diclofenac and naproxen. Patients making short-term use of NSAIDs had low compliance if they experienced adverse drug effects, whilst conversely in long-term users, those with high compliance reported more adverse drug effects. Calculated compliance did not vary with age although older patients (over 65 years) claimed in their questionnaires to be more compliant than younger patients. Half the patients reported good or complete symptom relief. Half of those questions (and two thirds of those with good or complete symptom relief) rated their NSAID as the best treatment they had received for their current condition. The frequency of gastrointestinal adverse events was higher in the young and the old, which correlated with the use of anti-ulcer drugs, and increased with the total number of medications used. NSAIDs are used for a wide-range of conditions. They give symptom relief to, and are perceived as effective by, most patients taking them.

Gastrointestinal safety profile of meloxicam: a meta-analysis and systematic review of randomized controlled trials

This article provides a systematic review of the frequency and severity of adverse gastrointestinal (GI) events among patients using meloxicam, a cyclooxygenase (COX)-2–selective nonsteroidal anti-inflammatory drug (NSAID). A MEDLINE search of English language articles from 1990–1998, a manual search of citations from primary trials and review articles, and a manual search of proceedings from international gastroenterology meetings were conducted. Randomized clinical trials comparing the frequency of GI adverse events for meloxicam versus non–COX-2–selective NSAIDs were selected. Specific data about the frequency of dyspepsia; perforations, ulcers, and bleeds (PUBs); and withdrawal of medication because of adverse GI events was also extracted. From a pool of 62 potentially relevant citations, 12 randomized trials were identified. All trials concerning symptomatic GI adverse events used the World Health Organization’s Adverse Reaction Terminology List (WHO-ARTL) to code adverse events. Patients using meloxicam had fewer GI adverse events compared with non–COX-2–selective NSAIDs (odds ratio = 0.64; 95% confidence interval [CI], 0.59–0.69). Patients using meloxicam experienced less dyspepsia (odds ratio = 0.73; 95% CI, 0.64–0.84), fewer PUBs (odds ratio = 0.52; 95% CI, 0.28–0.96), and less frequent discontinuation of NSAID because of adverse GI events (odds ratio = 0.59; 95% CI, 0.52–0.67) compared with non–COX-2 selective NSAIDs. Meloxicam, a COX-2–selective NSAID, appears to cause fewer adverse GI events than standard, non–COX-2–selective NSAIDs. However, the generalizability of these data may be limited by the low dose of meloxicam used in most trials and the use of the WHO-ARTL to code adverse events.

The gastroprotective effects of tizanidine: an overview

Tizanidine is an alpha 2-adrenergic receptor agonist with myospasmolytic action. It is indicated for the treatment of back pain as monotherapy or in combination with nonsteroidal anti-inflammatory drugs (NSAIDs). Published experimental and clinical studies suggest that tizanidine reduces the frequency of NSAID-induced gastrointestinal (GI) adverse effects. In animal experiments tizanidine reduced baseline and induced gastric acid secretion, reversed NSAID-induced changes in gastric mucosal and gastric fluid glycoprotein content, and reduced NSAID-induced gastric ulcers. In clinical studies the frequency of GI adverse events and the frequency of occult blood in stool were generally reduced when tizanidine was combined with an NSAID as compared with NSAID treatment alone. The mechanism of action is probably through reduction of gastric acid secretion and favorable effects on gastric glycoprotein content by means of stimulation of gastric and central alpha 2-adrenergic receptors. Experimental and clinical data supporting a gastroprotective effect of tizanidine are reviewed in this paper, and the possible mechanisms are discussed.

Comparison of the effects of acarbose and voglibose in healthy subjects

Acarbose and voglibose are alpha-glucosidase inhibitors. Although the pharmacologic effects and incidence of abdominal adverse events associated with the two drugs have been reported to differ, no study has directly compared acarbose and voglibose. To compare the pharmacologic effects and gastrointestinal adverse events associated with the two drugs, a randomized, placebo-controlled, double-masked, fivefold crossover study was performed in 20 healthy male subjects. To assess the pharmacologic effects, plasma immunoreactive insulin (IRI), plasma glucose, and 24-hour urinary connecting-peptide immunoreactivity (CPR) excretion were measured. Although the postprandial increase in plasma glucose level was reduced significant with both acarbose and voglibose, the rate of reduction was small. The maximum concentration (C max) and area under the plasma concentration—time curve (AUC) of plasma IRI after meals decreased significantly with all treatments except voglibose 0.3 mg compared with placebo. Overall, the C max and AUC of plasma IRI decreased more when subjects received acarbose than voglibose. Urinary CPR excretion decreased by 30.6% and 41.7%, respectively, in subjects who received acarbose 50 mg or 100 mg compared with the previous day when no drug was given, whereas the urinary CPR excretion did not decrease significantly with voglibose. There was no significant difference in the frequency of gastrointestinal adverse events between groups, including the placebo group. One-day administration of acarbose and voglibose at currently recommended clinical doses demonstrated that acarbose was more effective in sparing endogenous insulin secretion than was voglibose.