Empagliflozin: a new treatment option for patients with type 2 diabetes mellitus.

Empagliflozin is an oral sodium-glucose cotransporter 2 (SGLT2) inhibitor that reduces hyperglycemia in type 2 diabetes mellitus (T2DM) by decreasing renal glucose reabsorption and promoting urinary glucose excretion. In clinical trials, empagliflozin demonstrated significant improvements in glycemic control, as monotherapy and in combination regimens. In addition, empagliflozin was associated with weight loss and moderate reductions in blood pressure. In the EMPA-REG OUTCOME study, empagliflozin significantly reduced the risk of the composite primary endpoint of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke. Across the trials in general, empagliflozin was well tolerated, with no increased risk of hypoglycemia except when used with an insulin secretagogue or insulin. An increased risk of genital infections and urinary tract infections has been reported, although the association is less clear for urinary tract infections. Overall, empagliflozin appears to be a promising treatment for T2DM.

Impact of diabetes duration on hypoglycaemia in patients with type 2 diabetes treated with insulin glargine or NPH insulin.

AIM: To compare the impact of diabetes duration on hypoglycaemia in patients with type 2 diabetes mellitus (T2DM) treated with insulin glargine or NPH insulin. METHODS: A pooled analysis of 24-week patient level data from randomized controlled studies comparing once-daily insulin glargine with once-daily NPH insulin in insulin-naïve adult patients with T2DM was performed, stratifying patients into quartiles by duration of diabetes: <5.8 years; 5.8 to <9.2 years; 9.2 to <14 years and ≥14 years. Daytime and nocturnal hypoglycaemia events were evaluated. RESULTS: Data from 2330 patients in four randomized controlled trials were included in the analysis; 1258 treated with insulin glargine and 1072 with NPH insulin. The rates of daytime hypoglycaemia were similar for insulin glargine and NPH insulin, irrespective of disease duration. Patients with longer T2DM duration treated with glargine experienced greater glycated haemoglobin A1c (HbA1c) reductions. Rates of severe nocturnal hypoglycaemia and nocturnal hypoglycaemia [self-monitored blood glucose < 70 mg/dl (3.89 mmol/l) and < 50 mg/dl (2.78 mmol/l)] were all significantly and positively correlated with the duration of diabetes for patients treated with NPH insulin but not with insulin glargine. Despite improvements in HbA1c, rates of symptomatic nocturnal hypoglycaemia were significantly lower with insulin glargine than with NPH insulin in patients with longer T2DM duration. CONCLUSION: There is a lower risk for nocturnal hypoglycaemia with insulin glargine than with NPH insulin. When considering diabetes duration, insulin glargine (compared to NPH insulin) may be particularly beneficial in patients with a longer duration of T2DM.

Effects of pulsatile intravenous insulin therapy on the progression of diabetic nephropathy.

The purpose of this study was to assess the effects of pulsatile intravenous insulin therapy (PIVIT) on the progression of diabetic nephropathy in patients with type 1 diabetes mellitus (DM). This 18-month multicenter, prospective, controlled study involved 49 type 1 DM patients with nephropathy who were following the Diabetes Control and Complications Trial (DCCT) intensive therapy (IT) regimen. Of these, 26 patients formed the control group (C), which continued on IT, while 23 patients formed the treatment group (T) and underwent, in addition to IT, weekly PIVIT. Blood pressure in all patients was maintained below 140/90 mm Hg on antihypertensive medication, preferentially using angiotensin-converting enzyme (ACE) inhibitors. All study patients were seen in the clinic weekly for 18 months, had monthly glycohemoglobin (HbA1c), and every 3 months, 24-hour urinary protein excretion and creatinine clearance (CrCl) determinations. The HbA1c levels declined from 8.61% +/- 0.33% to 7.68% +/- 0.31% (P = .0028) in the T group and from 9.13% +/- 0.36% to 8.19% +/- 0.33% (P = .0015) in the C group during the study period. CrCl declined significantly in both groups, as expected, but the rate of CrCl decline in the T group (2.21 +/- 1.62 mL/min/yr) was significantly less than in the C group (7.69 +/- 1.88 mL/min/yr, P = .0343). We conclude that when PIVIT is added to IT in type 1 DM patients with overt nephropathy, it appears to markedly reduce the progression of diabetic nephropathy. The effect appears independent of ACE inhibitor therapy, blood pressure, or glycemic control.

Do estrogens improve bone mineral density in osteoporotic women over age 65?

A retrospective analysis of our experience with estrogen and fluoride treatment in 91 patients with postmenopausal osteopenia followed for 6-47 months has been performed. Treatment included calcium (1000 mg/day) and either conjugated estrogens (0.625 mg/day) or sodium fluoride (50 mg/day), or both. All patients had at least two serial dual-photon spinal bone mineral density measurements performed 6 months or more apart. Estrogen treatment was associated with increased bone mineral density (5.3%/year), as was fluoride alone (7.5%/year). Estrogen and fluoride together were additive (9.6%/year). In women over age 65 the estrogen effect was just as great (6.9%/year) as in younger women. Estrogen benefit occurred predominantly in the first 18 months of treatment (7.0%/year), after which time changes in bone mineral density were similar to those in untreated controls, who showed stable bone mineral density. We conclude that aggressive estrogen and fluoride treatment tailored to the severity of the individual's postmenopausal osteopenia results in short-term improvement in spinal bone mineral density. These data further support that elderly women respond to estrogen replacement therapy with absolute and relative increments in bone density similar to those in younger women.

Avoiding reoperation for indeterminate thyroid nodules identified as malignant after surgery.

Thyroid nodules that are indeterminate as carcinoma by needle biopsy before surgery and by study of frozen sections at the time of surgery are occasionally identified to be malignant in later studies. If only a lobectomy has been performed, the advisability of reoperation to remove the remaining thyroid tissue to facilitate radioactive iodine therapy may cause concern. To obviate this difficulty as well as to reduce the occurrence of nodules later in a preserved contralateral thyroid lobe and to provide additional thyroid tissue for study, contralateral subtotal or near total lobectomy has been performed for indeterminate thyroid nodules. The small remnant of remaining thyroid tissue can later be ablated by radioactive iodine if desired. Of 37 patients with indeterminate thyroid nodules, none required reoperation, although the diagnosis of carcinoma was established after surgery for eight patients, three of whom were treated with radioactive iodine.

Bone demineralization, a factor of increasing significance in the management of primary hyperparathyroidism.

The significance of bone demineralization was evaluated for 97 patients treated surgically for primary hyperparathyroidism since 1980. Of 31 patients studied by bone densitometry, 16 showed moderate to severe osteoporosis. In approximately 20% of the total group, bone demineralization, including a bone fracture problem in some, was the dominant or a major indication for operation. Serial bone studies in six patients taken preoperatively or in patients not operated on for primary hyperparathyroidism showed an average loss of bone mineral density of 0.9% per year, whereas in four patients treated surgically serial studies showed an average increase of 9.8% per year. Although estrogen intake reduced serum calcium levels, significant bone demineralization or fractures were present in four patients aged 40 to 59 years and in five patients more than 60 years of age who had taken estrogens for many years. We conclude that in primary hyperparathyroidism, bone demineralization (1) justifies surgical correction in a significant number of patients; (2) should be evaluated, especially in elderly women; (3) is not prevented by estrogen intake, which may instead confuse decision making; (4) is reversed after surgical correction, but suggestions of incomplete reversal emphasize importance of this factor; (5) should be considered in postoperative management; and (6) involves many variables.

Thyroid nodules indeterminate by needle biopsy.

In our experience with 121 patients 18 (15 percent) thyroid nodules studied by needle biopsy were considered indeterminate relative to the presence of a low-grade, well-differentiated carcinoma. For 11 of the 18 patients, operation was performed with carcinoma identified in two (18 percent). Although experience reduced this problem, the frequency of carcinoma justifies operation for patients with indeterminate thyroid nodules by needle biopsy, unless other factors dictate otherwise. Inadequate results of fine-needle aspiration biopsy requires a determination of therapy on the basis of other clinical factors. However, permanent disappearance or great reduction in size following aspiration of cystic nodules, repeat biopsy, and biopsy with large needles are important in supporting nonoperative therapy. The indeterminate and inadequate cases must be considered in assessing reports of the use of needle biopsy of thyroid nodules. The large size of a thyroid nodule and previous external radiation therapy are factors supporting operative treatment. Improved selection of patients with benign thyroid nodules for thyroid hormone suppression therapy is needed--thyroid-releasing hormone testing may be of help.

Homologous radioimmunoassay for human epidermal growth factor (urogastrone).

Epidermal growth factor (EGF), a polypeptide hormone originally discovered in the mouse submaxillary gland, stimulates growth in a variety of tissues in several species. This hormone has recently been identified in human urine. A homologous RIA for human EGF (RIA-hEGF) has been developed. In general, levels were similar to those recently reported using a heterologous RIA system. Twenty-four-hour urinary excretion of RIA-hEGF by normal adult males and females was 63.0 +/- 3.0 and 52.0 +/- 3.5 (mean +/- SE) micrograms/total vol, or 29.7 +/- 1.1 and 39.8 +/- 1.7 micrograms/g creatinine, respectively. Excretion by females taking oral contraceptives was significantly greater (60.1 +/- 2.7 micrograms/g creatinine; P less than 0.01) than that by females who were not. Recent evidence suggests the probable identity of hEGF and beta-urogastrone, a potent inhibitor of gastric acid secretion. Adult males with active peptic ulcer disease appeared to have lower urinary RIA-hEGF excretion (22.9 +/- 2.6 micrograms/g creatinine) than normal men, but this was not significant (P greater than 0.05). Several of those with very low values had histories of alcohol abuse. Excretion by patients with Cushing's syndrome was normal. Patients with psoriasis or recovering from major burns excreted both abnormally high and abnormally low levels of RIA-hEGF, with no obvious correlation to their clinical condition. There was no apparent diurnal or postprandial variation in urinary RIA-hEGF excretion by normal subjects. An excellent linear correlation was observed between RIA-hEGF and creatinine concentrations in each urine sample for each subject, suggesting that RIA-hEGF concentration in a random urine sample provides a valid index of 24-h RIA-hEGF excretion.