Will Oral Semaglutide be a Game-Changer in the Management of Type 2 Diabetes in Indian Context?

The glucagon-like peptide-1 receptor agonists (GLP-1RAs) have important beneficial effects on glycemic control and body weight along with their pleiotropic effects on various systems of the body. However, until now these agents were administered via an injection posing a challenge to patient convenience. Oral semaglutide is a first in class oral GLP-1RA co-formulated with an absorption enhancer for the treatment of type 2 diabetes mellitus (T2DM). The clinical efficacy and safety of oral semaglutide has been extensively evaluated in the Peptide InnOvatioN for Early diabEtes tReatment (PIONEER) program of clinical trials. This review shall elaborate on the unique diabetes situation in India and why the oral GLP-1RA (semaglutide) will be a game-changer in the Indian setting

Hyperglycemia in hospitalized patients of a tertiary care hospital: prevalence and treatment in two cross-sectional evaluations (2011-2020)

ABSTRACT Objective: A study at Centro Hospitalar Universitário do Porto in 2011 revealed suboptimal control of inpatient hyperglycemia and a similar one was carried out in 2020. This study compares the results of 2011 and 2020 regarding prevalence of hyperglycemia, metabolic control, treatment and glycemic profile by infection/non-infection diagnosis. Subjects and methods: We performed two cross-sectional studies on 13th December 2011 and 9th October 2020 that included all non-critical adults with at least 24 hours of hospitalization, with no specific intervention between them. Glycemic control evaluated by minimum and maximum capillary blood glucose (CBG) in the previous day categorized as hypoglycemia (<70 mg/dL), normoglycemia (70-179 mg/dL) and hyperglycemia (≥180 mg/dL) (SPSS v.20). Results: A total of 418 and 445 patients were respectively included in 2011 and 2020 studies and the prevalence of hyperglycemia was similar. Glycemic control improved numerically although not significantly in 2020: increase in normoglycemia, reduction in hyperglycemia and reduction in hypoglycemia. There was an increase in the use of basal-bolus regimens (19.6% vs. 7.3%, p = 0.009) and a decrease in human basal (p < 0.01) and rapid-acting insulin use (p = 0.001) with a proportional increase in long-acting (p = 0.002) and rapid-acting analogs (p < 0.001) use. There was a higher prevalence of infection (39.8% vs. 23.1%, p = 0.006) in 2020 and, in the infection subgroup, there were higher insulinization rates (37.3% vs. 10.7%, p = 0.017) and a trend to glycemic control improvement. Conclusion: Despite the higher insulinization rates, the preference for new insulin analogs and a trend to better glycemic control, we have not yet reached targets, so education still remains necessary.

Type 2 diabetes mellitus and heart failure: Hot topic report on 70th American College of Cardiology scientific annual meeting / 中华内分泌代谢杂志

Type 2 diabetes mellitus(T2DM) and heart failure (HF) often occur concomitantly and interact with each other, leading to poor prognosis and high mortality. T2DM is also an important risk factor for HF. Based on the relevant hot topics and late-breaking clinical trials of the 70th American College of Cardiology (ACC) scientific annual meeting, this paper elaborates on the importance of diabetes management and optimal management strategy for patients with diabetes and HF from aspects of epidemiology, the relationship between T2DM and HF, cardiovascular benefits of antihyperglycemic medication and evidence-based recommendations.

Sodium-glucose cotransporter-2 inhibitors: updated evidence on their efficacy and safety in patients with type-2 diabetes

Management of type-2 diabetes mellitus (T2DM) is challenging. The scope of existing therapies toward T2DM has transformed remarkably. These large assortments of therapies have produced evidence-based data. Sodium-glucose cotransporter-2 inhibitor (SGLT-2i) is the most recent class of oral anti-hyperglycemic agents. They are approved by Food and Drug Administration for the treatment of diabetes mellitus. SGLT-2i has a unique mechanism of action and that lower glucose independent of insulin. They reduce renal tubular glucose reabsorption, thereby lowering blood glucose without stimulating the release of insulin. Additional advantages involve suitable effects on blood pressure and weight. According to guidelines of the American Association of Clinical Endocrinologists/ the American College of Endocrinology 2016, SGLT-2i (in the form of canagliflozin, dapagliflozin, and empagliflozin) is one of the acceptable alternatives to metformin as initial therapy towards T2DM. Canagliflozin, dapagliflozin, and empagliflozin reduce the cardiovascular risk in comparison to placebo as the part of standard care. This review article focuses on the clinical trials published over the past year and specifically the metabolic aspect of SGLT-2i and the adverse effects related to SGLT-2 inhibitors.

Study on the Mechanism of Gegen Qinlian Decoction for Lowering Blood Lipids and Preventing Blood Glucose Increase Based on Intestinal Flora / 中国药房

OBJECTIVE：To study the ef fects of Gegen qinlian decoction （GGQLD）on blood lipid and blood glucose of hyperlipidemia（HLP）model rats ，and to explore its mechanism from the perspective of intestinal flora. METHODS ：Totally 48 rats were randomly divided into blank control group （n＝8）and modeling group （n＝40）. For consecutive 5 weeks，model group was given high-lipid diet to induce HLP model ；blank control group was given routine diet. After modeling ，30 modeling rats were randomly divided into model group ，simvastatin group （positive control ，10 mg/kg），GGQLD high-dose ，medium-dose and low-dose groups （14.85，4.95，1.65 g/kg，by crude drug ），with 6 rats in each group. Blank control group and model group were given constant volume of normal saline intragastrically ；administration groups were given relevant medicine intragastrically ，once a day，for consecutive 11 weeks. At the same time ，each group was continuously given corresponding diet. After the last medication ， body mass and body length of rats were determined ，and Lee ’s index was calculated. Serum levels of TG ，TC，HDL-C，LDL-C and fasting blood glucose （FBG）were determined in rats. DNA of rat caecum content was extracted for 16S rRNA V 3-V4 region sequencing. The Two-part model was used to analyze the correlation between intestinal flora with lipids and blood glucose. RESULTS：After 11 weeks of administration ，compared with blank control group ，the body mass ，body length ，Lee’s index ， serum levels of TC ，TG，HDL-C and FBG of model group were increased significantly （P＜0.05 or P＜0.01），while the level of HDL-C was decreased significantly （P＜0.05）. Compared with model group ，body mass and Lee ’s index and serum levels of TG ， FBG of rats in GGQLD high-dose group ，and serum levels of TC ，TG in GGQLD medium-dose group ，as well as serum level of TG of rats in GGQLD low-dose group was decreased significantly （P＜0.05 or P＜0.01）. Correlation analysis with intestinal flora showed that TC and TG shared 3 operational taxonomic units （OTU），including OTU 559，OTU701 and OTU 135（OTU135 was also shared with FBG ），which were all positively correlated with the level of TC ，TG and FBG （P＜0.01）. The three OTU were annotated as Tyzzerella of Spirillaceae ，Anaerotruncus of Verrucaceae and Peptoclostridium of Streptococcidae ，respectively. High-dose and low-dose GGQLD had a down-regulating effect on Tyzzerella and Anaerotruncus（P＜0.05 or P＜0.01），while had up-regulating effect on Peptoclostridium（P＜0.01）. CONCLUSIONS ：High-dose GGQLD （14.85 g/kg）can effectively reduce the body mass and blood lipid of HLP model rats ，and can prevent the abnormal increase of blood glucose of model rats. The mechanism may be associated with that the reduction of intestinal flora （Tyzzerella，Anaerotruncus）content.

Controlled clinical trial with the combination therapy with metformin, thiazolidinediones, glucagon-like peptide 1 analog in patients with type 2 diabetes and metabolic syndrome / 中华内分泌代谢杂志

Objective The aim of this study was to compare the efficacy and safety of metformin/thiazolidinediones (TZDs) / glucagon-like peptide 1 (GLP-1) analogs (triple therapy) with conventional glucose-lowering therapy ( conventional therapy ) for patients with type 2 diabetes and metabolic syndrome. Methods A prospective randomized-controlled 26-week study was carried out. A total of 82 patients with type 2 diabetes and metabolic syndrome were randomized to receive either triple therapy protocal or just conventional therapy, altogether with 41 cases in each group. Results HbA1C value was significantly reduced in triple therapy group versus the conventional therapy group [(2.23 ± 1.75)％ vs (1.48 ± 1.59)％, P<0.05]. Values of body mass index, waist circumference, and visceral fat area were significantly reduced in triple therapy group as compared to those of conventionaltherapygroup[(2.50±1.81vs0.92±1.82)kg/m2,(6.75±4.92vs1.66±3.25)cm,(24.10±19.10vs 10.02±20.10)cm2, all P<0.01, respectively]. Control rates of HbA1C and fasting plasma glucose for triple therapy were higher than those for conventional therapy ( both P<0. 05 ) . No hypoglycemia occurred in triple therapy group. Subjects receiving triple therapy experienced more frequent gastrointestinal side effects than those in conventional therapy group ( 18. 87％ vs 3. 92％, P<0. 05 ) . The most common side event was mild nausea ( 90％) . Conclusion Combination therapy with metformin/TZDs/GLP-1 analogs had statistically significant advantages in the control of body weight, waist circumference, and visceral fat area in addition to the control of blood glucose over conventional glucose-lowering therapy in our patient cohort, it seems to be an optimized therapeutic regimen for patients with type 2 diabete and metabolic syndrome.

Controlled clinical trial with the combination therapy with metformin, thiazolidinediones, glucagon-like peptide 1 analog in patients with type 2 diabetes and metabolic syndrome / 中华内分泌代谢杂志

Objective@#The aim of this study was to compare the efficacy and safety of metformin/thiazolidinediones (TZDs) / glucagon-like peptide 1 (GLP-1) analogs (triple therapy) with conventional glucose-lowering therapy(conventional therapy) for patients with type 2 diabetes and metabolic syndrome.@*Methods@#A prospective randomized-controlled 26-week study was carried out. A total of 82 patients with type 2 diabetes and metabolic syndrome were randomized to receive either triple therapy protocal or just conventional therapy, altogether with 41 cases in each group.@*Results@#HbA1C value was significantly reduced in triple therapy group versus the conventional therapy group [(2.23±1.75)% vs (1.48±1.59)%, P<0.05]. Values of body mass index, waist circumference, and visceral fat area were significantly reduced in triple therapy group as compared to those of conventional therapy group [(2.50±1.81 vs 0.92±1.82)kg/m2, (6.75±4.92 vs 1.66±3.25)cm, (24.10±19.10 vs 10.02±20.10)cm2, all P<0.01, respectively]. Control rates of HbA1C and fasting plasma glucose for triple therapy were higher than those for conventional therapy (both P<0.05). No hypoglycemia occurred in triple therapy group. Subjects receiving triple therapy experienced more frequent gastrointestinal side effects than those in conventional therapy group (18.87% vs 3.92%, P<0.05). The most common side event was mild nausea (90%).@*Conclusion@#Combination therapy with metformin/TZDs/GLP-1 analogs had statistically significant advantages in the control of body weight, waist circumference, and visceral fat area in addition to the control of blood glucose over conventional glucose-lowering therapy in our patient cohort, it seems to be an optimized therapeutic regimen for patients with type 2 diabete and metabolic syndrome.

Glucose-Lowering Agents in the Management of Nonalcoholic Fatty Liver Disease / 임상당뇨병

Nonalcoholic fatty liver disease (NAFLD) is more prevalent in diabetic patients than in non-diabetic subjects, because the two diseases share a common pathophysiological mechanism. Associated abnormalities can be observed from the pre-diabetic stage. Lifestyle intervention, including diet, exercise, and weight loss, is the primary recommended therapy for NAFLD. Among the therapeutic drugs for NAFLD treatment, anti-diabetic agents are aimed at improving or slowing the progression of NAFLD in addition to lowering blood glucose. In this paper, we systemically review the evidence surrounding antidiabetic medications and their ability to improve disease progression in patients with NAFLD.

Progress in pharmacological effects and clinical applications of berberine / 中国药理学与毒理学杂志

Berberine is an isoquinoline alkaloid isolated from Rhizoma Coptidis and Cortex Phellodendri,which has a long medical history in China.Recent studies have indicated that berberine has multiple pharmacological activities including anti-inflammatory,anti-microorganisms,anti-cancer,cardiac protection,glucose lowering,regulating lipid metabolism and immune suppression.Berberine has been used for the treatment of intestinal infectious diseases for many years.With the continuous progress of the research,it is reported that berberine has many new clinical applications,including treatment of the cardiovascular disease,metabolic syndrome and its complications,cancers,abdominal adhesions and chlamydia trachomatis infection.This review is intended to introduce the role of berberine in various aspects of pharmacological effects,molecular mechanisms and clinical applications.

Analysis of medication in patients with hypertension complicating T2DM in a hospital / 重庆医学

Objective To investigate the types of commonly used anti-hypertensive drugs and hypoglycemic drugs and treatment schemes to provide a basis for rationally treating hypertension complicating type 2 diabetes mellitus(T2DM).Methods The medication situation in 191 patients with hypertension complicating T2DM in our hospital were analyzed and investigated.The use of anti-hypertensive drugs and hypoglycemic drugs and treatment scheme were statistically analyzed.Results In 191 patients with hypertension complicating T2DM,the single drug use in the anti-hypertensive scheme accounted for 9.42 ％,two-drug combined use accounted for 64.91％,three-drug combined use for 17.8 ％ and four-drug combined use for 7.85 ％.The medication of ARB+CCB had the highest use frequency;the anti-hypertensive total effective rate was 96.86 ％.In the hypoglycemic schemes,the insulin use accounted for 30.37％,and the use frequency of metformin+ gliclazide was highest,the hypoglycemic total effective rate was 98.43％.Conclusion The medication for the patients suffering from hypertension complicating T2DM is relatively reasonable,and worth of being popularized and applied in clinical practice.

Biological activity studies of the novel glucagon-like peptide-1 derivative HJ07 / 中国天然药物

AIM@#To identify the glucose lowering ability and chronic treatment effects of a novel coumarin-glucagon-like peptide-1 (GLP-1) conjugate HJ07.@*METHOD@#A receptor activation experiment was performed in HEK 293 cells and the glucose lowering ability was evaluated with hypoglycemic duration and glucose stabilizing tests. Chronic treatment was performed by daily injection of exendin-4, saline, and HJ07. Body weight and HbA1c were measured every week, and an intraperitoneal glucose tolerance test was performed before treatment and after treatment.@*RESULTS@#HJ07 showed well-preserved receptor activation efficacy. The hypoglycemic duration test showed that HJ07 possessed a long-acting, glucose-lowering effect and the glucose stabilizing test showed that the antihyperglycemic activity of HJ07 was still evident at a predetermined time (12 h) prior to the glucose challenge (0 h). The long time glucose-lowering effect of HJ07 was better than native GLP-1 and exendin-4. Furthermore, once daily injection of HJ07 to db/db mice achieved long-term beneficial effects on HbA1c lowering and glucose tolerance.@*CONCLUSION@#The biological activity results of HJ07 suggest that HJ07 is a potential long-acting agent for the treatment of type 2 diabetes.

The influence of glucose-lowering rate on CKMB and muscle hemoglobin in type 2 diabetes mellitus with coronary heart disease / 中华内分泌代谢杂志

One hundred and fifty-one type 2 diabetic patients with coronary heart disease ( T2 DMC) and 142 cases of type 2 diabetes mellitus were included for analyzing the influence of different glucose-lowering rates on MB isoenzyme of creatine kinase (CKMB) and muscle hemoglobin level changes to search for the rational glucose-lowering rate.The level of CKMB in type 2 deabetes mellitus group was significantly lower( P＜0.05 ) at follow-up than that before and after intensive therapy.In type 2 diabetes mellitus group,when the fasting or postprandial glucose-lowering rate was not greater than 6 mmol· L-1 · d-1,the level of CKMB and muscle hemoglobin were significantly lower at follow-up than that before intensive therapy ( P＜0.05 ).When the fasting glucose-lowering rate is greater than 6 mmol· L-1 · d-1,the level of CKMB is significantly higher after intensive therapy than that before glucose-lowering ( P＜0.05 ).In T2DMC group,when the fasting or postprandial glucose-lowering rate was not greater than 4 mmol· L-1 · d-1,the level of CKMB and muscle hemoglobin was significantly lower at follow-up than that before intensive therapy(P＜0.05 or P＜0.01 ),buthigher at follow-up when the fasting glucose-lowering rate was greater than 4 mmol· L-1 · d-1(P＜0.05).

Blood glucose level and other biochemical changes induced in normal mice by oral Traditional Chinese Medicine complex for diabetes (TCM-D™)

Background: A number of Traditional Chinese Medicine (TCM) preparations are being used for the treatment of diabetes mellitus. Some components of these preparations have biochemical effects other than those of lowering blood glucose and indeed have been used for other medical indications in traditional practice. The primary objective of the study was to determine the effect of the oral mixture of Traditional Chinese Medicine for diabetes (TCM-D™ complex) on blood glucose level and the biochemical changes if any, on the liver (ALT, AST, gamma-GT, albumin, globulin) and renal (blood creatinine, urea) functions in normal mice. The oral mixture is an aqueous extract of four wellknown traditional Chinese medicinal herbs and consists of Trichosanthes kirilowii Maxim., Paeonia lactiflora Pall.,Glycyrrhiza uranlensis Fisch., and Panax ginseng (red) CA Meyer in the proportion of 36%, 28%, 18%, and 18% respectively of the dry weight. These herbs have been shown to have blood glucose lowering activity and have been used for other traditional medicinal purposes. The safety of the combination was evaluated in the present study. Methods: Experimental Balb/c mice were treated orally via gastric tube with the extract at daily doses equivalent to 1 and 10 times the recommended human dose for 8 weeks. Blood glucose and other biochemical profiles were monitored at pre-treatment and monthly posttreatment until killed. Results: When compared to pre-treatment levels, the blood glucose levels were significantly lower in treated animals compared to those in the control group. At the recommended TCM-D™ dose the levels in treated animals were significantly lower than that of control animals and at pre-treatment. When compared with pre-treatment, the glucose levels were lowest at Week 8 of treatment, the mean levels being 111.23%, 83.32% and 70.33% in control, and in animals given 1 x and 10 x the recommended TCM-D™ dosage respectively. The blood glucose lowering effect was also associated with a significant weight loss in treated animals. There were transient increases in AST and ALT levels but these reverted to normal at Week 8 of treatment. The levels of bilirubin, g-GT, albumin, creatinine and blood urea were also not significantly different at Week 8 from pre-treatment levels in all groups. Conclusion: Even at 10 times the dosage recommended for humans, TCM-D™ did not affect the liver and renal functions of treated animals. Treated and control animals remained healthy and normal throughout the period of observation.

Changes of high sensitive-C reactive protein and cardiac troponin I levels in patients with type 2 diabetes during glucose-lowering therapy / 中华内分泌代谢杂志

Objective To compare the changes of high sensitive-C reactive protein (hs-CRP) and cardiac troponin Ⅰ ( cTn Ⅰ ) levels before and after intensive therapy in patients with type 2 diabetes,and to find out the reasonable glucose-lowering rate.Methods One hundred and thirty-two cases of type 2 diabetes( T2DM group) and 135 cases of type 2 diabetes with coronary heart disease( T2DM+CHD group) received intensive therapy.After testing hs-CRP and cTn Ⅰ levels,the variations were analyzed.Results The ranges of the change in cTn Ⅰ and hs-CRP levels were different under four glucose-lowering rates in the T2DM+CHD group( P＜0.05 ).cTn Ⅰ and hs-CRP levels were higher than those before intensive therapy in the T2DM+CHD group with glucose-lowering rate greater than 4.0mmol· L-1 · d-1.The other two subgroups with glucose-lowering rate less than 4.0 mmol· L-1 · d-1 showed decreased cTn Ⅰ and hs-CRP levels.While at the end of 3 months follow-up,cTn Ⅰ and hs-CRP levels were all significantly lower than those before intensive therapy in four subgroups ( P＜0.05 ).Conclusions The increase of cardiovascular events after intensive therapy may be due to excessively fast glucose-lowering rate.The reasonable glucose-lowering rate for patients with type 2 diabetes should depend on whether there is accompanying coronary heart disease.For type 2 diabetes with coronary heart disease,excessively fast glucose-lowering rate could lead to acute rise ofcTn Ⅰ and hs-CRP levels,which causes myocardial injury.The mechanism of myocardial injury resulted from excessively fast glucose-lowering rate may be due to activation of the inflammatory pathway.In type 2 diabetes with coronary heart disease,long-term good control of blood glucose could alleviate inflammatory response and cardiac damage resulted from excessively fast glucose-lowering rate.

Influence of glucose-lowering rate on left ventricular function in type 2 diabetes mellitus patients with coronary heart disease / 中华内分泌代谢杂志

Objective To explore the influence of glucose-lowering rate on left ventricular function in patients with type 2 diabetes mellitus (T2DM). Methods One hundred and thirty-two cases of type 2 diabetes mellitus and 135 cases of type 2 diabetes mellitus with coronary heart disease (T2DM+CHD)received intensive glucose lowering therapy. Then, after measuring left ventricular ejection fraction (LVEF) and E/A ratio, the variation was analyzed. Results LVEF was significantly higher than that before intensive therapy in T2DMsubgroup with glucose-lowering rate less than 6 m mol · L-1 · d-1( P＜0.05 ). So was T2DM+CHD subgroup with glucose-lowering rate less than 4 mmol· L-1 · d-1 (P＜0.05). LVEF was significantly lower than that before intensive therapy in T2DM+CHD subgroup with glucose-lowering rate greater than 4 mmol · L-1 · d-1( P＜0. 05 ),while by the end of following up for 3 months, LVEF stepped up and no significant difference was observed between subgroups ( P ＞ 0. 05 ). The E/A ratio stepped up in both subgroups after intensive therapy ( P ＜ 0. 05 ).Conclusions For T2DM patients with coronary heart disease, excessively fast glucose-lowering rate may impair left ventricular function. Long-term good control of blood glucose restores the impaired left ventricular function causes by excessively fast glucose-lowering rate. After intensive therapy, left ventricular diastolic function finally improves in both subgroups regardless of the glucose-lowering rate and coronary heart disease.

A new trend on type 2 diabetes mellitus therapy—six key-points of glucose-lowering methods / 中国实用内科杂志

Although the medicial sciences greately developed nowadays,diabetes mellitus(DM) which acts as a whole-life disease,remains a difficult problem to overcome.And it is a great challenge of lowering glucose levels effectively,preventing and postponing the onset of chronic complications to improve the quality of DM patients’ life.For better glycemic control,the writer who has many years of clinical experiences on DM therapy,combined results of several large-scale clinical trials,and then summarised the new trends of lowering glucose levels effectively,that is,"SELECT",which means sixkey points of glucose-lowering.