Comparing the efficacy and safety of different analgesic strategies after open hemorrhoidectomy: a systematic review and network meta-analysis.

PURPOSE: To evaluate the clinical efficacy and safety of different analgesic interventions in the treatment of pain after open hemorrhoidectomy by systematic review and network meta-analysis. METHODS: Randomized controlled trials that met the inclusion criteria in PubMed, Cochrane Library, Embase, Web of Science, Scopus, CNKI, WANFANG DATA, and VIP were searched from the date of database construction to June 28, 2022. RESULTS: Among the 13 randomized controlled trials (RCTs), 731 patients were included in the network meta-analysis. Most interventions are more effective than placebo in relieving postoperative pain. 24 h postoperative Visual Analogue Scale (VAS): glyceryl trinitrate (GTN) (mean difference (MD) - 4.20, 95% CI - 5.35, - 3.05), diltiazem (MD - 1.97, 95% CI - 2.44, - 1.51), botulinum toxin (BT) (MD - 1.50, 95% CI - 2.25, - 0.75), sucralfate (MD - 1.01, 95% CI - 1.53, - 0.49), and electroacupuncture (EA) (MD - 0.45, 95% CI - 0.87, - 0.04). 48 h postoperative VAS: diltiazem (MD - 2.45, 95% CI - 2.74, - 2.15), BT (MD - 2.18, 95% CI - 2.52, - 1.84), and sucralfate (MD - 1.41, 95% CI - 1.85, - 0.97). 7 d postoperative VAS: diltiazem (MD - 2.49, 95% CI - 3.20, - 1.78) and sucralfate (MD - 1.42, 95% CI - 2.00, - 0.85). The first postoperative defecation VAS: EA (MD - 0.70, 95% CI - 0.95, - 0.46). There are few data on intervention safety, and additional high-quality RCTs are expected to study this topic in the future. CONCLUSION: Diltiazem ointment may be the most effective medication for pain relief following open hemorrhoidectomy, and it can dramatically reduce pain within one week of surgery. The second and third recommended medications are BT and sucralfate ointment. GTN has a significant advantage in alleviating pain 24 h after open hemorrhoidectomy, but whether it causes headache is debatable; thus, it should be used with caution. EA's analgesic efficacy is still unknown. There was limited evidence on the safety of the intervention in this study, and it was simply presented statistically.

Efficacy of Diltiazem to Improve Coronary Vasomotor Dysfunction in ANOCA: The EDIT-CMD Randomized Clinical Trial.

BACKGROUND: Diltiazem is recommended and frequently prescribed in patients with angina and nonobstructive coronary artery disease (ANOCA), suspected of coronary vasomotor dysfunction (CVDys). However, studies substantiating its effect is this patient group are lacking. OBJECTIVES: The randomized, placebo-controlled EDIT-CMD (Efficacy of Diltiazem to Improve Coronary Microvascular Dysfunction: A Randomized Clinical Trial) evaluated the effect of diltiazem on CVDys, as assessed by repeated coronary function testing (CFT), angina, and quality of life. METHODS: A total of 126 patients with ANOCA were included and underwent CFT. CVDys, defined as the presence of vasospasm (after intracoronary acetylcholine provocation) and/or microvascular dysfunction (coronary flow reserve: <2.0, index of microvascular resistance: ≥25), was confirmed in 99 patients, of whom 85 were randomized to receive either oral diltiazem or placebo up to 360 mg/d. After 6 weeks, a second CFT was performed. The primary end point was the proportion of patients having a successful treatment, defined as normalization of 1 abnormal parameter of CVDys and no normal parameter becoming abnormal. Secondary end points were changes from baseline to 6-week follow-up in vasospasm, index of microvascular resistance, coronary flow reserve, symptoms (Seattle Angina Questionnaire), or quality of life (Research and Development Questionnaire 36). RESULTS: In total, 73 patients (38 diltiazem vs 35 placebo) underwent the second CFT. Improvement of the CFT did not differ between the groups (diltiazem vs placebo: 21% vs 29%; P = 0.46). However, more patients on diltiazem treatment progressed from epicardial spasm to microvascular or no spasm (47% vs 6%; P = 0.006). No significant differences were observed between the diltiazem and placebo group in microvascular dysfunction, Seattle Angina Questionnaire, or Research and Development Questionnaire 36. CONCLUSIONS: This first performed randomized, placebo-controlled trial in patients with ANOCA showed that 6 weeks of therapy with diltiazem, when compared with placebo, did not substantially improve CVDys, symptoms, or quality of life, but diltiazem therapy did reduce prevalence of epicardial spasm. (Efficacy of Diltiazem to Improve Coronary Microvascular Dysfunction: A Randomized Clinical Trial [EDIT-CMD]; NCT04777045).

Diltiazem-associated Photodistributed Hyperpigmentation.

Diltiazem is a calcium-channel blocker commonly used for the treatment of hypertension. Common adverse effects include dizziness, headache, and edema. Fewer than 20 cases of diltiazem-associated photodistributed hyperpigmentation have been reported in the literature. Here, we present the case of a 71-year-old woman with new-onset facial hyperpigmentation 6 months after initiating treatment with diltiazem.

Acute Airway Inflammation Caused By Incomplete Ingestion of Extended-Release Diltiazem: A Case Report.

BACKGROUND: Diltiazem in its extended-release formulation is widely prescribed and is generally well-tolerated. Currently, there are no published case reports of localized inflammation related to extended-release diltiazem causing either significant pill esophagitis or airway inflammation when swallowed incompletely. CASE REPORT: We present a case of an 85-year-old female who reported difficulty swallowing roughly 18 h after incomplete ingestion of an extended-release diltiazem tablet. She had mild stridor and visible right-sided neck swelling on examination. Imaging revealed a large inflammatory mass, which was believed to be a subacute to chronic neoplastic process when reviewed both by radiology and otolaryngology. Two days after presentation, however, the patient's symptoms and the inflammatory mass had resolved entirely. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Extended-release diltiazem can cause an inflammatory mass when ingested incompletely, leading to possible acute airway compromise. Any invasive airway intervention should be approached with caution, given the degree of acute inflammation. Even in patients who do not require intervention, close observation until clinical improvement is warranted in symptomatic patients with a history of recent incomplete ingestion of extended-release diltiazem.

Topical Minoxidil Versus Topical Diltiazem for Chemical Sphincterotomy of Chronic Anal Fissure: A Prospective, Randomized, Double-Blind, Clinical Trial.

BACKGROUND: Anal fissure is a common anorectal problem causing severe pain and discomfort to the patients. Chemical sphincterotomy has emerged as a noninvasive alternative to the surgical methods of fissure treatment. The objective of this study was evaluation of the efficacy and the adverse effects of topically applied minoxidil in chemical sphincterotomy of chronic anal fissure in comparison with topical diltiazem. METHODS: A total of 88 patients with chronic anal fissure aged between 15 and 65 years were included in this double-blind, randomized clinical trial and were randomly assigned to either 0.5% minoxidil cream or 2% diltiazem cream twice daily for 2 weeks. The pain intensity, bleeding, wound healing, itching, headache, dizziness, significant drop in blood pressure, allergy and fissure relapse were assessed on a monthly basis for 2 months. RESULTS: Both diltiazem and minoxidil reduced the pain, bleeding and improved fissure healing with no significant difference. There were no between-groups differences in the frequencies of adverse effects, except for itching which was slightly higher with minoxidil during the first month. Allergy occurred in two patients in the minoxidil group, which was not severe and did not lead to discontinuation of the trial. CONCLUSION: Topically administered minoxidil is of equal efficacy as diltiazem in the treatment of chronic anal fissure with low frequency of adverse effects. Thus, it can be considered as an agent for chemical sphincterotomy of anal fissure, but the itching at the beginning of the treatment can affect the adherence of the patient to treatment. Trial registration number IRCT2015041414483N6 (the full trial protocol could be accessed online at www.irct.ir ).

Ischemic Acute Tubular Necrosis due to Diltiazem Overdose.

Diltiazem overdose has a high mortality rate due to cardiotoxicity associated with bradycardia and hypotension. A previous article reported that this type of overdose can cause acute tubular necrosis, which was not pathologically, but rather clinically, diagnosed. We herein report the case of a 55-year-old man who sustained nonoliguric acute kidney injury after taking 60 diltiazem tablets. A kidney biopsy performed six days after admission showed ischemic, not toxic, acute tubular necrosis. The patient's kidney function improved spontaneously. In this case report, we clarify the cause of renal impairment caused by diltiazem overdose pathologically. Physicians should therefore consider ischemic acute tubular necrosis as a cause of kidney injury in patients with diltiazem overdose.

Calcium channel blockers and risk of breast cancer: a meta-analysis of 17 observational studies.

PURPOSE: Studies on the association between the use of calcium channel blockers (CCBs) and breast cancer risk have reported inconsistent results. We quantitatively assessed this association by conducting a meta-analysis based on the evidence from observational studies. METHODS: We searched PubMed, MEDLINE, EMBASE and the Cochrane Library for relevant studies published up to and including December 31, 2013. We calculated pooled risk ratios (RRs) for cancer risk. RESULTS: A total of 17 studies (9 cohort studies, 8 case-control studies) were selected for further study. These studies included 149,607 female subjects, of which 53,812 were CCBs users, who were followed for 2-16 years. The risks of breast cancer among patients receiving CCBs were significantly different for the pooled RRs (95% confidence interval) of cohort studies 1.08 (0.95, 1.20) and case-control studies 0.98 (0.86, 1.09). Differences were also noted for cancer risk, for CCBs use of <5 years 0.96 (0.78, 1.15), and for >5 years 1.01 (0.74, 1.28), as well as for ever used 1.08 (0.95, 1.20), and for current use 1.13 (0.83, 1.42). The RR for studies longer than 10 years was 1.71 (1.01, 2.42), and for studies evaluating nifedipine was 1.10 (0.87, 1.33) and diltiazem was 0.75 (0.40, 1.10). CONCLUSIONS: The long-term use of CCBs appears to have a significant relationship with breast cancer. Well-designed clinical trials are needed to optimize the doses and types of these drugs needed to minimize their carcinogenic potential.

Comparative efficacy and usefulness of acebutolol and diltiazem for the prevention of atrial fibrillation during perioperative time in patients undergoing pulmonary resection.

BACKGROUND: Postthoracic surgery atrial fibrillation (AF) is the most frequently occurring arrhythmia. Strategies for preventing AF have been amply evaluated, but currently there are no clearly defined guidelines for treatment of AF after thoracic surgery. METHODS: The study was prospective and randomized controlled trial. Acebutolol and diltiazem versus placebo were compared, among 117 patients postpneumonectomy or lobectomy at the Thoracosurgery Clinic, Poznan University of Medical Sciences in Poland. Patients who were enrolled in the study were randomly assigned to one of the three groups: those who received acebutolol (Group 1) or diltiazem (Group 2) and compared with patients without antiarrhythmic drugs (Group 0). Each group consisted of 39 patients. The patients were continuously monitored postoperatively with 24 ECG (Holter monitor) in the intensive care unit. RESULTS: In patients receiving acebutolol AF occurred in 5% compared with 23% of patients receiving diltiazem and 20% of patients receiving placebo (difference not statistically significant). CONCLUSIONS: Acebutolol and diltiazem appear to have been non-effective for the treatment or prevention of AF. Side effects were mild. In comparison to diltiazem, however, acebutolol had a beneficial effect on the circulatory system. Patients who had received acebutolol proved to have had fewer tachycardia episodes and supraventricular ectopy during the postoperative period. It seems that acebutolol can be useful, especially in patients with sympathetic activity dominance.

Topical diltiazem vs. topical glyceril trinitrate in the treatment of chronic anal fissure: a prospective, randomized, double-blind trial.

BACKGROUND AND STUDY AIMS: Chemical sphincterotomy is a new way for the treatment of chronic anal fissure which avoids the risk of faecal incontinence associated with traditional surgical methods. The aim of this study was to compare topical Diltiazem with topical Glyceril trinitrate in the treatment of chronic anal fissure. PATIENTS AND METHODS: 61 patients (10 Male, 51 Female) between 16-81 years of age with chronic anal fissure were included in this prospective, randomized, double-blind trial. The patients were randomly allocated to either Diltiazem gel (2%) or Glyceril trinitrate ointment (0.2%) and were asked to use the treatment twice daily for 8 weeks. Each patient was reviewed every two weeks; pain scores, healing and side effects were assessed. RESULTS: Healing occurred in 33 of 36 (91.66%) patients treated with Diltiazem after 6 weeks and 15 of 25 (60%) patients treated with Glyceril trinitrate after 8 weeks which shows a significant difference in favour of Diltiazem (P < 0.001). The rest of the patients were either non-compliant or did not heal and underwent surgery. Headache occurred in all of the patients treated with Glyceril trinitrate but none of the patients treated with Diltiazem developed headache. The frequency of other side-effects was also less in patients treated with Diltiazem (P < 0.001). CONCLUSIONS: Diltiazem gel was found to be superior to Glyceril trinitrate ointment due to significantly higher healing rate and fewer side-effects.

Topical diltiazem cream versus botulinum toxin a for the treatment of chronic anal fissure: a double-blind randomized clinical trial.

OBJECTIVE: A double-blind randomized clinical trial to compare topical diltiazem with botulinum toxin A (BTA) in the treatment of chronic anal fissure. BACKGROUND: Chronic anal fissures remain a challenging condition. Topical diltiazem and BTA are promising agents in the treatment of anal fissure. As to date diltiazem and BTA were never compared in a solid randomized trial, which is the purpose of this study. METHODS: One hundred thirty-four patients were randomized to receive either diltiazem cream and placebo injection or BTA injection and placebo cream. The primary end point was fissure healing after 3 months. RESULTS: After 3 months healing of the fissure was noted in 32 of 74 (43%) patients in the diltiazem group and 26 of 60 (43%) patients in the BTA group. Reduction >50% in mean pain score was noted in 58 of 74 (78%) patients in the diltiazem group and 49 of 60 (82%) patients in the BTA group. Perianal itching was the only side effect reported and was noted in 15% of patients in the diltiazem group, and this difference was statistically significant (P = 0.012). CONCLUSIONS: BTA yields higher healing rates in the short term, though after 3 months diltiazem and BTA resulted in equal healing rates. Also no significant difference in pain reduction was observed for both treatments. This study shows no significant advantage of one treatment compared to the other. This randomized clinical trial is registered by the Dutch Trial Register as NTR1012.

Facial hyperpigmentation caused by diltiazem hydrochloride.

Diltiazem hydrochloride, a member of the calcium channel blocker family of antihypertensive medications, has been found to produce many cutaneous reactions, such as photodistributed hyperpigmentation. We report a 53-year-old black woman who presented with facial darkening that began 6 months after starting diltiazem. Areas were not responsive to topical bleaching creams. Biopsy showed postinflammatory pigment alteration with a largely burned-out lichenoid dermatitis. The results of all laboratory evaluations were negative, including complete blood cell count, antinuclear antibodies, anti-Ro antibodies, and anti-La antibodies. Patch testing and photo-patch testing to numerous drugs including diltiazem were negative. Phototesting revealed a normal minimal erythema dose to UVA but a slightly reduced minimal erythema dose to UVB. Diltiazem was then stopped and hydralazine hydrochloride was started. While UVA has been thought to be the main culprit in drug-induced photosensitive reactions, this case demonstrates that UVB may possibly play a role in diltiazem-induced photodistributed hyperpigmentation.

Topical diltiazem hydrochloride and glyceryl trinitrate in the treatment of chronic anal fissure.

OBJECTIVE: To compare the symptomatic relief, healing and side-effects of topical diltiazem (DTZ) and glyceryl trinitrate in the treatment of chronic anal fissure. STUDY DESIGN: Randomized controlled trial. PLACE AND DURATION OF STUDY: The Surgical Outpatient Department of Civil Hospital, Karachi, from March 2006 to February 2007. METHODOLOGY: Patients with chronic anal fissure were included in the study and randomized to two groups. One group was administered topical 2% diltiazem hydrochloride and other was given 0.2% glyceryl trinitrate (GTN), perianally twice daily for 8 weeks. Patients with anal fissure due to other diseases like inflammatory bowel disease, malignancy, sexually transmitted diseases, previous treatment with local ointment or surgery; patients who required anal surgery for any concurrent disease like hemorrhoids, pregnant women and patients with significant cardiovascular conditions were excluded. There were four follow-up sessions during the course of treatment. Healing and side-effects were recorded. Analysis was done by SPSS version 10 on intention-to-treat basis. Chi-square was used where appropriate. RESULTS: Eighty patients with symptomatic chronic anal fissure were included in the study and equally divided into two groups. After 8 weeks of treatment healing occurred in 31 of 40 patients treated with diltiazem and 33 of 40 patients treated with GTN (p = 0.576). There were less side-effects with DTZ (n=13) than with GTN (n=29, p < 0.001]. In particular, headache occurred more commonly with GTN (n=27) than with DTZ (n=9, p < 0.0001). CONCLUSION: Diltiazem hydrochloride and glyceryl trinitrate were equally effective in healing chronic anal fissure. Diltiazem caused fewer side-effects particularly headache than glyceryl trinitrate ointment. Diltiazem may be the first-line treatment for chemical sphincterotomy for the chronic anal fissure.

[Efficacy and safety of topical diltiazem 2 % in anal fissure]. / Efectividad y seguridad de diltiazem 2 % tópico en fisura anal.

OBJECTIVES: To evaluate the effectiveness and safety of 2 per cent diltiazem ointment in the treatment of anal fissure. To analyse the relationship between healing and diagnosis, and duration of the treatment and the number of applications. METHODS: A prospective observational study of all patients diagnosed with anal fissure that began treatment with topical diltiazem between January and June in 2007. Diltiazem ointment was prepared in the Pharmacy Service. Effectiveness and safety were assessed by a telephone survey conducted with each patient after 8 weeks of treatment, adding it to the patient's clinical records. The variables that were analysed were healing, adverse effects, diagnosis, duration of treatment and number of applications, among others. Follow-up was carried out for up to one year until complete healing of the fissure. The data analysis was carried out by descriptive statistics, crosstabs and Chi-square. RESULTS: A total of 70 patients were included in the study and anal fissure healed in 48.6 % of them. Healing occurred in 54.5 % of patients with anal fissure and in 33.3 % of patients with anal fissure and haemorrhoids. Some adverse effects occurred in 30 % of patients. Therapy was abandoned due to adverse reactions for 5.7 %. The fissure was cured for 60 % of patients who underwent treatment for a month or more. More than twice-daily applications did not lead to improved healing. There were no significant statistical differences in these results. CONCLUSIONS: Despite not having found statistical differences between the analysed variables, treatment of anal fissures with 2 per cent diltiazem ointment has avoided surgery in nearly 50 % of patients, with few adverse effects.

Diltiazem-induced eosinophilic pleural effusion.

A 68-year-old woman developed eosinophilic pleural effusion and systemic eosinophilia 2 months after starting antihypertensive therapy with diltiazem. Several drugs are known to cause this disorder; however, the only other drug the patient had been taking was clonidine, which she had taken for the past 3-4 years. She was evaluated for all other possible causes of eosinophilia and eosinophilic pleural effusion, including malignancy, infection, and autoimmune disorders. Her symptoms resolved after diltiazem was discontinued, and no recurrence was noted on follow-up. To our knowledge, this is the first case report of eosinophilic pleural effusion caused by diltiazem. According to the Naranjo adverse drug reaction probability scale, a probable relationship existed between diltiazem and the patient's eosinophilia and pleural effusion. Although numerous drugs have been associated with eosinophilia and eosinophilic pleural effusion, the spectrum may actually be wider than is commonly thought and may include such unrecognized agents as diltiazem.

Diltiazem induces severe photodistributed hyperpigmentation: case series, histoimmunopathology, management, and review of the literature.

BACKGROUND: Diltiazem hydrochloride is a commonly prescribed benzothiazepine calcium channel blocker for the treatment of cardiovascular disease. Recently, 8 cases of diltiazem-induced photodistributed hyperpigmentation occurring predominantly in elderly African American women were reported. Here, we report occurrence for the first time in a light-skinned African American woman and a Hispanic woman. We also report this finding in an African American man. Biopsy specimens of hyperpigmented areas were obtained for histopathologic evaluation and marker studies. Photospectrometry analysis for diltiazem was performed to analyze the photoabsorption properties of this drug. OBSERVATIONS: Routine laboratory examination results were normal in all patients. Serologic test results for antinuclear antibodies, including Sjögren antibodies anti-Ro (SS-A) and anti-La (SS-B), were negative. Histopathologic analysis of the skin biopsy specimens revealed a sparse lichenoid infiltrate, prominent pigmentary incontinence, and numerous melanophages in the dermis. There was no increase in dermal mucin suggestive of lupus. The mononuclear cells in the specimens were strongly positive for CD3, weakly positive for CD68, and either weakly positive or negative for CD79a. All specimens were negative for Alcian blue staining. Photospectrometry analysis of diltiazem showed an absorption range within the UV-B spectrum. CONCLUSIONS: Photospectrometry analysis revealed diltiazem could demonstrate a photosensitizing effect within the UV-B range. Discontinuation of therapy with diltiazem is the most effective modality in resolving hyperpigmentation. Avoidance of sun exposure and consistent use of sunscreens and sun-protective clothing are indicated for patients undergoing diltiazem therapy.

Intestinal pseudo-obstruction caused by diltiazem in a neutropenic patient.

OBJECTIVE: To describe a case of diltiazem-induced intestinal pseudo-obstruction in a neutropenic patient. CASE SUMMARY: A 74-year-old male with newly diagnosed acute myelogenous leukemia developed atrial fibrillation on day 12 of induction chemotherapy. He was initially treated with diltiazem 5 mg intravenously every 5-10 minutes for 5 doses and an amiodarone 150-mg loading dose intravenously. Diltiazem 30 mg orally 4 times daily and amiodarone continuous infusion were started thereafter. Amiodarone therapy was discontinued after one day due to an untoward adverse effect. The diltiazem dose was then escalated. By day 14, the patient was receiving diltiazem 120 mg orally 4 times daily. On day 15, he developed increasing abdominal distention with hyperactive bowel sounds. On day 16, a radiographic examination showed multiple dilated loops of both the small and large bowel representing possible intestinal pseudo-obstruction; diltiazem was discontinued that day. Starting on day 18, the patient showed recovery of intestinal pseudo-obstruction without intervention. No further GI complications developed during his remaining hospital course. DISCUSSION: Intestinal pseudo-obstruction is usually associated with underlying medical conditions such as trauma, infection, cardiac disease, and after surgery. Medications rarely cause such a condition. Detailed examination of the patient's record indicated neither infection nor other medications contributed to the development of intestinal pseudo-obstruction. Additionally, a radiographic examination ruled out neutropenic enterocolitis, a common gastrointestinal complication in neutropenic patients. Use of the Naranjo probability scale indicated a probable relationship between pseudo-obstruction and diltiazem in this patient. CONCLUSIONS: Although calcium-channel blockers rarely cause intestinal pseudo-obstruction, clinicians must be aware of this serious but reversible adverse effect.

Cross-comparison of patch test and lymphocyte proliferation responses in patients with a history of acute generalized exanthematous pustulosis.

An adverse cutaneous reaction to a systemically administered drug may rarely manifest as acute generalized exanthematous pustulosis (AGEP). Several recent reports have documented positive patch test results in patients with a history of AGEP, while two have demonstrated drug-specific in vitro lymphocyte proliferative responses. These findings suggest that drug-specific T cells mediate AGEP. We describe two patients with a history of AGEP who each demonstrated positive patch test results specific for the inciting drug: Patient #1 to the antibiotic metronidazole, and Patient #2 to the calcium channel-blocker diltiazem. Histologic examination of biopsy specimens taken from the patch test sites of these patients revealed spongiotic dermatitis and perivascular lymphocytes consistent with a delayed-type hypersensitivity reaction, rather than demonstrating subcorneal neutrophilic pustules more typical of AGEP. In vitro testing by measuring peripheral T cell proliferative responses to chemically purified drug correlated with the clinical response. In a direct cross-comparison, patch test results were shown to correlate with in vitro lymphocyte proliferative responses in two patients with a history of AGEP to different drugs. These findings provide additional evidence that the pathogenesis of AGEP involves a T cell-mediated immune response.

Comparison of the metabolic and antioxidant effects of diltiazem and vitamin E on streptozotocin-diabetic rats.

In this study, solitary and combined effects of vitamin E and the calcium-channel blocker diltiazem were investigated in streptozotocin (STZ)-induced diabetic rats. Thirty male Wistar albino rats, weighing approximately 200 g were used. Diabetes mellitus was induced by a single intravenous injection of STZ at a dose of 65 mg/kg body weight. Five experimental groups were established as STZ-diabetic, STZ-diabetic + vitamin E, STZ-diabetic + diltiazem and STZ-diabetic + vitamin E + diltiazem. Vitamin E was injected intraperitoneally three times a week at a dose of 500 mg/kg body weight. Diltiazem was given orally every day at a dose of 25 mg/kg body weight. At the end of the study (10 weeks) blood glucose levels of diabetic rats, which had received vitamin E and diltiazem, had significantly decreased when compared with untreated diabetic rats (P < 0.02). Similarly, HbA1c levels had significantly decreased in diabetic rats which had received vitamin E (P < 0.05), diltiazem (P < 0.01) and vitamin E + diltiazem (P < 0.02) when compared with untreated diabetic rats. Liver glutathione levels of diabetic rats, which had received vitamin E (P < 0.01) and vitamin E + diltiazem (P < 0.05) had significantly increased when compared with untreated diabetic rats. Liver lipid peroxide levels had significantly decreased in diabetic rats, which had received vitamin E (P < 0.001) and diltiazem (P < 0.01). With respect to their metabolic and antioxidant effects, vitamin E proved superior to diltiazem.