EFFICACY OF EARLY GLARGINE PLUS STANDARD IV INSULIN VERSUS STANDARD IV INSULIN IN PATIENTS WITH DIABETIC KETOACIDOSIS: A RANDOMISED CONTROLLED TRIAL - NIL

Start Date30 Sep 2024

Sponsor / Collaborator-

NCT06340854 / RecruitingPhase 3

A Study to Evaluate the Efficacy and Safety of Once-weekly Insulin Icodec When Switching From Daily Basal Insulins Compared to Once-daily Insulin Glargine U100 in Adults With Type 2 Diabetes

This study compares insulin icodec, a new insulin taken once a week, to insulin glargine, an insulin taken once a day. The study medicine will be investigated in participants with type 2 diabetes. Participants will either get insulin icodec or insulin glargine. Which treatment participants get is decided by chance. Insulin icodec is the new medicine being tested, while insulin glargine is already approved and can be prescribed by doctors. Participants will get one injection of insulin icodec once a week, or one injection of insulin glargine once a day, depending on the treatment group participants are assigned into. Participants will use a pen with a small needle to inject the medicine under participants skin into participants thigh, upper arm or stomach.The study will last for about 9 months, but participants will only be taking the study medicine for 6 months.

Start Date19 Apr 2024

Sponsor / Collaborator

Novo Nordisk A/S

NCT06619301 / RecruitingPhase 3IIT

Randomized Controlled Trial of Glargine Versus Neutral Protamine Hagedorn Insulin for the Treatment of Diabetes Mellitus in Pregnancy

We are asking you to take part in this research study because you are diagnosed with pregestational Type 2 Diabetes Mellitus or Gestational Diabetes Mellitus requiring insulin therapy in pregnancy. Currently, many hospitals differ among use of insulin for management of DM in pregnancy, with NPH, glargine and detemir being the most commonly used forms of basal insulin. Outside of pregnancy, NPH is rarely used with glargine and determir being the more common forms of insulin used due to their fewer episodes of hypoglycemia in these patients. Detemir has been well studied in pregnancy and found to be noninferior to NPH. Unfortunately, glargine has not been as well studied in pregnancy. Thus, with this study we want to compare glargine and NPH.
The purpose of this study is to compare two different forms of insulin (Glargine and NPH) that we regularly use to manage diabetes mellitus in pregnancy.

Start Date01 Apr 2024

Sponsor / Collaborator

Loyola University Medical Center

100 Clinical Results associated with Insulin glargine (Sanofi)

100 Translational Medicine associated with Insulin glargine (Sanofi)

100 Patents (Medical) associated with Insulin glargine (Sanofi)

2,107

Literatures (Medical) associated with Insulin glargine (Sanofi)

01 Nov 2024·DIABETES CARE

A Glycemic Threshold Above Which the Improvement of β-Cell Function and Glycemia in Response to Insulin Therapy Is Amplified in Early Type 2 Diabetes: The Reversal of Glucotoxicity

Article

Author: Ye, Chang ; Emery, Alexandra ; Kramer, Caroline K. ; Pu, Jiajie ; McInnes, Natalia ; Harris, Stewart B. ; Zinman, Bernard ; Retnakaran, Ravi ; Reichert, Sonja M. ; Gerstein, Hertzel C.

OBJECTIVE:

Alleviation of unrecognized glucotoxicity, with resultant recovery of β-cell function, could amplify the glucose-lowering effect of pharmacotherapy and contribute to the variable therapeutic response observed among patients with type 2 diabetes (T2D). However, clinical evidence supporting this concept is lacking. Short-term intensive insulin therapy (IIT) can ameliorate glucotoxicity and improve β-cell function in early T2D. Thus, for evidence of recovery of glucotoxicity-associated β-cell dysfunction, we sought to determine whether there exists a baseline fasting glucose threshold above which the post-IIT improvement in both β-cell function and glycemia is amplified.

RESEARCH DESIGN AND METHODS:

IIT (glargine, lispro) was administered for 3 weeks to 108 adults with T2D (mean duration 1.8 ± 1.4 years). Oral glucose tolerance tests before and after IIT enabled assessment of β-cell function by Insulin Secretion-Sensitivity Index-2 and insulinogenic index/HOMA-insulin resistance. For each level of baseline fasting glycemia from 6.0 to 10.5 mmol/L, we modeled the difference in IIT-induced percentage change in β-cell function between those at/above the indicated glucose level and those below it.

RESULTS:

The relationship between baseline fasting glucose and the differential change in β-cell function was nonlinear. Instead, this relationship was best fit by a cubic regression model with inflection (amplification) at fasting glucose at 9.3 mmol/L. Moreover, baseline fasting glucose at 9.3 mmol/L also identified the inflection point at which nonlinear reductions in fasting glucose and 2-h glucose, respectively, were both amplified.

CONCLUSIONS:

The respective improvements in β-cell function and glycemia in response to short-term IIT are amplified in those in whom baseline fasting glucose exceeds a defined threshold, consistent with reversal of glucotoxicity.

01 Nov 2024·Lancet Diabetes & Endocrinology

Continuous glucose monitoring-based metrics and the duration of hypoglycaemia events with once-weekly insulin icodec versus once-daily insulin glargine U100 in insulin-naive type 2 diabetes: an exploratory analysis of ONWARDS 1

Article

Author: Ásbjörnsdóttir, Björg ; Lingvay, Ildiko ; Mader, Julia K ; Bergenstal, Richard M ; Nishida, Tomoyuki ; Watt, Sara K ; Rosenstock, Julio

BACKGROUND:

Continuous glucose monitoring (CGM) can provide a comprehensive assessment of glycaemic control. This exploratory analysis of the ONWARDS 1 trial assessed CGM-based metrics and CGM-derived hypoglycaemia duration in insulin-naive individuals with type 2 diabetes treated with subcutaneous once-weekly insulin icodec (icodec) versus once-daily insulin glargine U100 (glargine U100).

METHODS:

ONWARDS 1 was a 78-week (52-week main treatment phase and a 26-week treatment extension phase plus a 5-week follow-up), randomised, open-label, treat-to-target, phase 3a trial done at 143 sites (outpatient clinics and hospital departments) across 12 countries. Adults (aged ≥18 years) with type 2 diabetes (HbA_1c: 7·0-11·0%) who had not previously received insulin were randomly assigned (1:1) via an interactive web-response system to once-weekly icodec or once-daily glargine U100. Double-masked CGM data were collected during treatment initiation (weeks 0-4), midtrial (weeks 22-26), end of main phase (weeks 48-52), end of extension phase (weeks 74-78), and follow-up (weeks 78-83). Secondary and exploratory outcomes were CGM-based metrics, including the mean percentages of time in glycaemic range (TIR; sensor glucose 3·9-10·0 mmol/L [70-180 mg/dL]), time in tight range (TITR; 3·9-7·8 mmol/L [70-140 mg/dL]), time above range (TAR; >10·0 mmol/L [>180 mg/dL]), and time below range (TBR; <3·9 mmol/L [<70 mg/dL] and <3·0 mmol/L [<54 mg/dL]), and CGM-derived hypoglycaemic episode durations (episodes defined by sensor glucose <3·9 mmol/L [<70 mg/dL for ≥15 consecutive minutes]). Analyses were done in the full analysis set (all randomly assigned participants). The ONWARDS 1 trial is registered with ClinicalTrials.gov, NCT04460885, and is complete.

FINDINGS:

Participants were enrolled and randomly assigned in ONWARDS 1 between Nov 25, 2020, and Dec 1, 2022 (n=492 in each treatment group). During treatment initiation, we observed no statistically significant differences in the mean percentages of TIR, TITR, TAR, and TBR with icodec versus glargine U100. During the midtrial, end of main phase, and end of extension phase periods, the mean percentages of TIR and TITR were statistically significantly greater and the mean percentages of TAR statistically significantly lower with icodec versus glargine U100. The mean percentages of TIR met the internationally recommended CGM target (>70%) with icodec but not with glargine U100 during the three periods. TBR (<3·9 mmol/L [<70 mg/dL] and <3·0 mmol/L [<54 mg/dL]) was low and below recommended targets (<4% and <1%, respectively) across all study periods in both treatment groups, with no statistically significant differences between treatment groups for the lower threshold (<3·0 mmol/L [<54 mg/dL]). During the follow-up period, mean percentages of TIR, TITR, TAR, and TBR did not statistically significantly differ with icodec versus glargine U100. The duration of overall hypoglycaemic episodes was similar between treatment groups throughout the trial (median duration ≤35 min).

INTERPRETATION:

These CGM data support the long-term efficacy and safety of icodec versus glargine U100 during treatment and indicated no increase in the duration of individual hypoglycaemic episodes with icodec versus glargine U100 in insulin-naive individuals with type 2 diabetes.

FUNDING:

Novo Nordisk.

01 Nov 2024·DIABETES RESEARCH AND CLINICAL PRACTICE

Improved treatment satisfaction with once-weekly insulin icodec compared with once-daily basal insulin in individuals with type 2 diabetes: An analysis of patient-reported outcomes and participant interviews from ONWARDS 2 and 5 and a physician survey from ONWARDS 1

Article

Author: Benamar, Malik ; Meller Donatsky, Anders ; Philis-Tsimikas, Athena ; Franek, Edward ; Goldenberg, Ronald ; Davies, Melanie ; Polonsky, William ; Carstensen, Lisbeth ; Kellerer, Monika

AIMS:

The ONWARDS phase 3a clinical trials evaluated once-weekly insulin icodec (icodec) versus once-daily basal insulin in type 2 diabetes. This analysis investigated the treatment-related experiences of participants from ONWARDS 5 and 2, and physicians from ONWARDS 1.

METHODS:

Patient-reported outcomes were only collected during ONWARDS 5 (icodec with a dosing guide app vs. once-daily basal analogues) and 2 (icodec vs. once-daily insulin degludec). ONWARDS 1 (icodec vs. once-daily insulin glargine U100) physicians' treatment preferences and satisfaction were obtained via an online survey.

RESULTS:

In ONWARDS 5 and 2, there was a statistically significantly greater increase in total treatment satisfaction from baseline to end of treatment for icodec/icodec with app versus once-daily comparators, mostly driven by participants' willingness to continue and recommend treatment. In ONWARDS 2, 93.7 % of icodec users preferred once-weekly over once-daily basal insulin, mainly owing to less frequent injections and ease of use. ONWARDS 1 physicians reported greater satisfaction with once-weekly than with once-daily basal insulin and were more likely to recommend once-weekly injections.

CONCLUSIONS:

These results demonstrate improved treatment satisfaction with, and strong preferences for, once-weekly versus once-daily basal insulin. Treatment convenience and willingness to continue and recommend once-weekly basal insulin treatment were highlighted.

CLINICAL TRIAL REGISTRATIONS:

ONWARDS 1: NCT04460885; ONWARDS 2: NCT04770532; ONWARDS 5: NCT04760626.

News (Medical) associated with Insulin glargine (Sanofi)

15 Oct 2024

·pipelinereview.com

Gan & Lee Pharmaceuticals' Three Innovative Drugs: GZR18 Injection, GZR4 Injection, and GZR101 Injection Achieve Primary Endpoints in Phase 2 Clinical Studies

BEIJING, China I October 15, 2024 I Recently, Gan & Lee Pharmaceuticals (Gan & Lee, Shanghai Stock Exchange: 603087) announced that three of its independently developed drugs — the bi-weekly GLP-1 receptor agonist GZR18 injection, the once-weekly basal insulin analog GZR4 injection, and the premixed dual insulin analog GZR101 injection — successfully achieved positive results in three Phase 2 clinical trials conducted in adult patients with Type 2 diabetes (T2D) in China. In these studies, Gan & Lee’s three innovative drugs demonstrated superior or comparable efficacy in lowering glycated hemoglobin (HbA1c) compared to the respective positive comparator drugs separately. Gan & Lee Pharmaceuticals’ Diabetes Product Portfolio Diagram Statement: 1. GZR18, GZR4, and GZR101 are investigational drugs that have not yet been approved in China. 2. Gan & Lee Pharmaceuticals does not recommend the use of any unapproved drugs/indications. GZR18 Injection: a Phase 2 Study evaluate the Efficacy and Safety of GZR18 Injective vs. Semaglutide (Ozempic ® ) in Chinese Patients with Type 2 Diabetes The Phase 2b clinical trial (CTR20232069) is a multicenter, randomized, open-label study comparing the efficacy and safety of GZR18 injection versus semaglutide (Ozempic ® ) in Chinese adult T2D patients with poor glycemic control on lifestyle interventions and/or unregulated use of anti-diabetic drugs, and on oral anti-diabetic treatment for at least three months. A total of 264 subjects were recruited across 25 clinical centers in China. Patients were randomized to receive bi-weekly GZR18 injections (12 mg, 18 mg, or 24 mg) or once-weekly 24 mg GZR18 injections, or 1 mg semaglutide for 24 weeks, including the dose-escalation period. The primary efficacy endpoint was the change in HbA1c from baseline after 24 weeks of continuous treatment. The subjects had a mean diabetes history of 11-18 years, and baseline HbA1c ranged from 8.28% to 8.56%. After 24 weeks of treatment, the mean HbA1c reduction from baseline in the GZR18 groups was as follows: 1.87% (12 mg, bi-weekly), 2.28% (18 mg, bi-weekly), 1.94% (24 mg, bi-weekly), and 2.32% (24 mg, once-weekly), all higher than the semaglutide group (1.60% reduction)*. Additionally, in treatment-naïve patients with poor glycemic control on lifestyle interventions, the HbA1c reduction in the bi-weekly GZR18 injection group reached 2.98%, compared to 2.04% in the semaglutide group, with a significant HbA1c reduction (p < 0.05)*. After 24 weeks of treatment, patients in the bi-weekly GZR18 group experienced a maximum weight loss of 5.42 kg, compared to 3.25 kg in the semaglutide group*. GZR18 also greatly improved fasting glucose, blood pressure, and lipid levels, etc, providing comprehensive benefits for diabetic patients. GZR18 was generally well-tolerated, with safety and tolerability consistent with known GLP-1 receptor agonists. The most common adverse events were gastrointestinal-related, and no severe hypoglycemic events were observed. GZR4 Injection: a Phase 2 Study Comparing the Efficacy and Safety of GZR4 injection vs. insulin degludec (Tresiba ® ) in Chinese Patients with Type 2 Diabetes The Phase 2 trial (CTR20232431) was a multicenter, randomized, open-label, parallel-group study evaluating the efficacy, tolerability and safety of once-weekly GZR4 injections versus once-daily insulin degludec (Tresiba ® ) in 83 T2D patients with poor glycemic control on oral antidiabetic drugs (Part A) and 96 T2D patients with poor glycemic control on a combination of oral antidiabetic drugs and basal insulins (Part B). In part A, the mean HbA1c reduction of once-weekly GZR4 injection was 1.50%, comparable to insulin degludec’s reduction of 1.48%. In part B, GZR4 injection demonstrated a superior HbA1c reduction of 1.26%, compared to -0.87% for insulin degludec (treatment difference: -0.38%, p < 0.01)*. In addition, improvements in time-in-range (TIR) were comparable between GZR4 and insulin degludec. In this study, GZR4 injection showed good safety and tolerability, with no severe hypoglycemic events observed. GZR101 Injection: a Phase 2 Study Comparing the Efficacy and Safety of GZR101 injection vs. insulin degludec/insulin aspart (Ryzodeg ® ) in Chinese Patients with Type 2 Diabetes The Phase 2 clinical trial (CTR20232431) is a multicenter, randomized, open-label, parallel-controlled, treat-to-target Phase 2 study. Part A of the study aimed to compare the efficacy, safety, and tolerability of GZR101 injection administered once-daily versus insulin degludec/insulin aspart (Ryzodeg ® ) administered once-daily over 16 weeks in 62 patients with uncontrolled T2D on oral anti-diabetic drugs. In Part B, the study compared the efficacy, safety, and tolerability of GZR101 injection combined with insulin aspart versus insulin degludec/insulin aspart (Ryzodeg ® ) administered twice-daily over 16 weeks in 91 patients with uncontrolled T2D on basal/premixed insulin. In Part A, the HbA1c levels in the once-daily GZR101 injection group decreased by 1.56%, superior to the -1.31% reduction in the once-daily insulin degludec/insulin aspart group (treatment difference: -0.24%). In Part B, GZR101 injection combined with insulin aspart achieved HbA1c reductions of -1.64% (once-daily insulin aspart) and -1.68% (twice-daily insulin aspart), both higher than the -1.59% reduction in the twice-daily insulin degludec/insulin aspart group (treatment differences of -0.06% and -0.09%, respectively)*. Moreover, GZR101 injection demonstrated comparable efficacy to insulin degludec/insulin aspart in controlling fasting and postprandial blood glucose, as well as improving time-in-range (TIR). In this trial, GZR101 injection showed good safety and tolerability. The estimated incidence of hypoglycemic events in both groups did not show statistically significant differences during the study. *The trial results are presented as least squares means (LS mean). Note: severe hypoglycemia is defined as Grade 3 hypoglycemia (serious events without specific plasma glucose boundaries, with conscious and/or somatic changes, hypoglycemia requiring help from others). Dr. Zhong-ru Gan, Chairman of Gan & Lee Pharmaceuticals, stated: “The positive results achieved by GZR18, GZR4, and GZR101 in Phase 2 clinical trials mark an important milestone in improving the current landscape of diabetes treatment. These results demonstrate that our three products provide better glycemic control compared to similar antidiabetic drugs. Over the years, we have successfully launched a full range of insulin products, from human insulin to insulin analogs, covering both basal and mealtime insulin, in the hope of comprehensively meeting the treatment needs of different diabetes patients. With recent breakthroughs in our research and development, we have also expanded our product portfolio with oral antidiabetic drugs, filling a gap in this critical area. Focusing on the frontiers of the endocrine field, we are actively promoting the development of new drugs, aiming to achieve comprehensive management of chronic metabolic diseases, including diabetes and obesity. Gan & Lee’s product portfolio currently covers next-generation insulin based on the extension to emerging metabolic disease targets, such as GLP-1 receptor agonists, supporting patients throughout their treatment journey with a view to driving changes in the management of diabetes and metabolic diseases and improving the quality of life of patients.” Forward-Looking Statements: These forward-looking statements are based on expectations and assumptions as of the date of this release. Due to various factors, actual results may differ significantly. We do not undertake any obligation to update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise. Reference 1. WANCAI XING, WEI CHEN, YINING ZHANG, JING GAO, ANSHUN HE, JUN ZHANG, YING DENG, FANGKAI XUE, YONGCHUN WANG, HAO FU, RUNYAO ZHANG, JINHUI HUANG, ZHONGRU GAN; 823-P: Molecular and Pharmacological Properties of GZR4, a Once-Weekly Insulin Analog. Diabetes 14 June 2024; 73 (Supplement_1): 823–P. https://doi-org.libproxy1.nus.edu.sg/10.2337/db24-823-P About Gan & Lee Gan & Lee Pharmaceuticals developed the first Chinese domestic insulin analog. Currently, Gan & Lee has six core insulin products, including five insulin analog varieties: long-acting glargine injection (Basalin ® ), fast-acting lispro injection (Prandilin™), fast-acting aspart injection (Rapilin ® ), mixed protamine zinc lispro injection (25R) (Prandilin™25), aspart 30 injection (Rapilin ® 30), and one human insulin injection – mixed protamine human insulin injection (30R) (Similin ® 30). The company has two approved medical devices in China, namely reusable insulin injection pen (GanleePen), and disposable pen needle (GanleeFine ® ). In China’s 2024 National Insulin-Specific Centralized Procurement, Gan & Lee Pharmaceuticals ranked first among all selected companies in terms of procurement demand for insulin analogs. The company is also making strides in international markets, with the disposable pen needle (GanleeFine ® ) approved by the US Food and Drug Administration (FDA) in 2020 and received GMP inspection approval from the European Medicines Agency (EMA) in 2024. These achievements significantly boost Gan & Lee’s competitiveness in both international and domestic markets. In the future, Gan & Lee will strive for comprehensive coverage in diabetes treatment. Moving forward with its mission to become a world-class pharmaceutical company, Gan & Lee will also actively develop new chemical entities and biological drugs, focusing on treatments for metabolic diseases, cardiovascular diseases, and other therapeutic areas. Further Information: BPRD@ganlee.com (Media) BD@ganlee.com (Business Development) info.medical@ganlee.com (Medical Information) SOURCE: Gan & Lee Pharmaceuticals

Clinical ResultPhase 2Drug Approval

27 Sep 2024

·endpts.com

Novo Nordisk to decrease some insulin pen manufacturing, transition supply

Novo Nordisk has told government and global nonprofits that it plans to significantly downsize its manufacturing of some of its insulin pens, according to one of the groups, and will transition a portion of its global supply to insulin vials and syringes that are easier to make but less convenient for patients. The company’s plans were disclosed in recent discussions with Doctors Without Borders, who described them to Endpoints News , as well as the WHO, the Australian government, and other governments and regulators. “We are not halting production of insulin in pens,” Novo said in an email to Endpoints. “In some cases, we will no longer make human insulin available in pens. It will be made available in a vial and disposable syringe.” While some countries, like Australia and South Africa, are now seeking alternatives, the full extent of Novo’s plans isn’t immediately clear. The company declined to comment further to Endpoints on exactly which markets would be affected. And it said that some — but not all — insulin pens would be affected by the shift. And it emphasized that the changes would happen slowly, over a period of years. While South Africa in June announced shortages of insulin pens due to Novo’s decision to deprioritize their manufacture and supply, Doctors Without Borders’ pharmacist coordinator Christina Cepuch told Endpoints Friday that the latest announcement would go much further, based on the company’s comments to the groups. Geneva-based Doctors Without Borders is also known as Médecins Sans Frontières, or MSF. The WHO lists Novo’s insulin pens on its essential medicines list , and will also have to find alternatives, Cepuch said. The WHO did not immediately respond to a request for comment. “What does the WHO do about this? There’s not going to be any left. I mean, Lilly makes these, but they don’t make large volumes,” Cepuch said. “And what is WHO going to tell member states? Change everyone to glargine pens or go back to vials?” Glargine is a form of long-acting insulin, and Novo is currently in the process of phasing out its own long-acting insulin, called Levemir. On Tuesday, the Therapeutic Goods Administration, Australia’s drug regulator, released a short notice saying Novo will discontinue “some of its earlier generation insulin products” over the next two years. Scant on details, the notice said Australia is looking into alternatives. Novo emphasized to Endpoints that it is expanding its overall drug manufacturing significantly with the acquisition of Catalent and other new investments. Earlier this week, the Danish company’s CEO Lars Fruergaard Jørgensen testified before the US Senate at a hearing on drug prices and was asked by Sen. Tammy Baldwin (D-WI) about its insulin manufacturing plans. Baldwin asked Jørgensen if he would commit to “continue to have a focus on providing critical insulin. You will not reduce your manufacturing capacity in that area.” “The world market for insulin is actually declining, so there’s less demand,” Jørgensen responded. “But we are committed to supply to the patient that has been using our insulin for years also into the future.” Cepuch suggested that the company might decide to use freed-up pen capacity for its GLP-1 obesity products, which are also in shortage, or other insulins. Novo said the insulin and GLP-1 pens are different.

14 Sep 2024

·www.prnewswire.com

Gan & Lee Pharmaceuticals Presented Two Positive Clinical Results of Once-weekly Insulin GZR4 at the 60th Annual Meeting of the European Association for the Study of Diabetes (EASD 2024)

In Phase Ia clinical study, GZR4 demonstrated favorable safety and tolerability profiles in healthy subjects, maintaining a stable glucose-lowering effect for up to one week with a single administration. In Phase Ib clinical study, patients with Type 2 diabetes mellitus (T2DM) receiving six weeks of GZR4 treatment were safe and well tolerated. GZR4 also exhibited improvements in fasting blood glucose (FBG), glycated hemoglobin (HbA1c), and time in range (TIR) across all dosage groups, outperforming the insulin degludec (IDeg) group. BEIJING, Sept. 14, 2024 /PRNewswire/ -- Gan & Lee Pharmaceuticals (Gan & Lee, Shanghai Stock Exchange: 603087) announced the clinical results from two Phase I trials of the Company's independently developed novel once-weekly insulin analog, GZR4, in healthy Chinese subjects and patients with T2DM in oral presentation and short oral discussion at the 60th Annual Meeting of the European Association for the Study of Diabetes (EASD 2024). Statement: 1. GZR18 injection is an investigational drug and has not yet been approved in China. 2. Gan & Lee Pharmaceuticals does not recommend the use of any unapproved drugs/indications. Phase Ia Study Results This placebo-controlled and active-comparator-controlled, single-center, single-dose, randomized, dose-escalation study aimed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of GZR4 in healthy adult male participants. The study was conducted following a dose-escalation design, starting from lower doses and progressively increasing to higher doses. Participants in cohorts 1-4 randomly receiving a subcutaneous injection of GZR4 (1, 3, 6, or 12 nmol/kg) or placebo, while cohort 5 received a single dose of 0.4 U/kg (2.4 nmol/kg) insulin degludec (IDeg) as an active comparator. A 24-hour glucose clamp procedure was conducted on days 2 and 7 respectively post-GZR4 administration in cohorts 2-4, and on day 1 post-IDeg administration in cohort 5. GZR4 exhibited favorable safety and tolerability in healthy subjects, with no serious adverse events (SAEs) reported, and no discontinuations due to the investigational product-related adverse events. PD results indicated that the glucose infusion rate (GIR) on day 7 was approximately 80% of that on day 2 in subjects receiving 12 nmol/kg GZR4, indicating that the glucose-lowering effect of GZR4 persists for approximately one week. Meanwhile, the area under the GIR-time curve on day 2 (AUCGIR,24-48h) and day 7 (AUCGIR,144-168h) for the 6 nmol/kg dose of GZR4 was similar to the 24-hour GIR (AUCGIR,0-24h) for the 0.4 U/kg (2.4 nmol/kg) of IDeg (37.84 ± 9.86 versus 40.60 ± 14.39 h*mg/kg/min, respectively)*, implying that the average daily glucose-lowering effect of GZR4 is comparable to that of IDeg. Convert accordingly, it is estimated that the potency of GZR4 is approximately 2.5-fold greater than that of IDeg when evaluating based on a similar molar concentration. Phase Ib Study Results In this randomized, open-label, active-controlled, multi-center, dose-escalation Phase Ib trial, a total of 36 patients with T2DM who had previously been treated with basal insulin were randomized in a 3:1 ratio to receive a fixed once-weekly dose of GZR4 (6, 8, or 12 nmol/kg) or once-daily (IDeg) (equal to the pre-enrolment daily basal insulin dosage) for 6 weeks. PK results showed that the maximum plasma concentration (Cmax) of GZR4 increased dose-dependently, while the time to maximum concentration (Tmax) and half-life were approximately 32 hours and 135 hours at steady state, respectively. PD data indicated dose-dependent reductions in FBG (-1.77 ± 0.20, -2.03 ± 0.66, and -2.75 ± 0.71 mmol/L for GZR4 in 6, 8, and 12 nmol/kg groups, respectively) in week 6, which outperformed the IDeg group (-1.12 ± 0.36 mmol/L*). After 6 weeks of treatment, the 6 nmol/kg GZR4 group demonstrated a reduction in HbA1c of 0.76 ± 0.14%, compared to the reduction of 0.13 ± 0.21% * in the IDeg group. In patients with T2DM, GZR4 demonstrated good safety and tolerability. No serious adverse events were reported in all treatment groups; the most frequently reported treatment-emergent adverse event was hypoglycaemia, but no severe hypoglycemia occurred. The detailed results of the Phase I studies will be published in a peer-reviewed journal. *Trial data are presented as mean ± standard error. Gan & Lee Pharmaceuticals also announced announced that a multicenter, randomized, open-label, parallel-control, treat-to-target phase 2 study is underway in patients with T2DM who have inadequate glycemic control with oral antidiabetic drugs, including insulin-naïve patients and patients on basal insulin. The study enrolled 179 adult participants and compares the efficacy and safety of once-weekly GZR4 with once-daily insulin degludec. All participants have completed treatment, and preliminary results are promising, further validating the findings from the Phase I studies. Dr. Gan Zhong-ru, Chairman of Gan & Lee Pharmaceuticals, commented: "A significant number of patients with Type 2 diabetes mellitus are experiencing delays in initiating insulin therapy and exhibit poor long-term adherence to treatment,etc. The introduction of weekly insulin preparations has the potential to significantly improve the aforementioned challenges. The completed Phase I trials confirmed GZR4's ability to provide stable glycemic control for a full week with a single dose, along with favorable safety and tolerability profiles. In addition, GZR4 is expected to reduce the weekly dosage of insulin required reaching the glycemic target, thereby reducing the possible risk of hypoglycaemia. We look forward to continuing to explore the clinical benefits of GZR4 in future trials." About Gan & Lee Gan & Lee Pharmaceuticals developed the first Chinese domestic insulin analog. Currently, Gan & Lee has six core insulin products, including five insulin analog varieties: long-acting glargine injection (Basalin®), fast-acting lispro injection (Prandilin™), fast-acting aspart injection (Rapilin®), mixed protamine zinc lispro injection (25R) (Prandilin™25), aspart 30 injection (Rapilin®30), and one human insulin injection - mixed protamine human insulin injection (30R) (Similin®30). The company has two approved medical devices in China, namely reusable insulin injection pen (GanleePen), and disposable pen needle (GanleeFine®). In China's 2024 National Insulin-Specific Centralized Procurement, Gan & Lee Pharmaceuticals ranked second overall and first among domestic companies in terms of procurement demand for insulin analogs. The company is also making strides in international markets, with the disposable pen needle (GanleeFine®) approved by the US Food and Drug Administration (FDA) in 2020 and received GMP inspection approval from the European Medicines Agency (EMA) in 2024. These achievements significantly boost Gan & Lee's competitiveness in both international and domestic markets. In the future, Gan & Lee will strive for comprehensive coverage in diabetes treatment. Moving forward with its mission to become a world-class pharmaceutical company, Gan & Lee will also actively develop new chemical entities and biological drugs, focusing on treatments for metabolic diseases, cardiovascular diseases, and other therapeutic areas. Forward-looking statements Forward-looking statements are based on our expectations and assumptions as of the date of the statements. Actual results may differ materially from those expressed in these forward-looking statements due to a variety of factors, and we can give no assurance that such results will be achieved in the future. We undertake no obligation to update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise. Further Information: [email protected] (Media) [email protected] (Business Development) [email protected] (Medical Information) SOURCE Gan & Lee Pharmaceuticals WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 1Clinical ResultDrug ApprovalPhase 2

100 Deals associated with Insulin glargine (Sanofi)

External Link

KEGG	Wiki	ATC	Drug Bank
D03250	Insulin glargine (Sanofi)	A10AE04	DB00047

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Diabetes Mellitus	EU	Sanofi-Aventis Deutschland GmbH	09 Jun 2000
Diabetes Mellitus	IS	Sanofi-Aventis Deutschland GmbH	09 Jun 2000
Diabetes Mellitus	LI	Sanofi-Aventis Deutschland GmbH	09 Jun 2000
Diabetes Mellitus	NO	Sanofi-Aventis Deutschland GmbH	09 Jun 2000
Diabetes Mellitus, Type 1	US	Sanofi-Aventis U.S. LLC	20 Apr 2000
Diabetes Mellitus, Type 2	US	Sanofi-Aventis U.S. LLC	20 Apr 2000

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Indication	Highest Phase	Country/Location	Organization	Date
Acute myocardial infarction	Phase 3	US	Sanofi	01 Apr 2008
Acute myocardial infarction	Phase 3	AR	Sanofi	01 Apr 2008
Acute myocardial infarction	Phase 3	BR	Sanofi	01 Apr 2008
Acute myocardial infarction	Phase 3	CA	Sanofi	01 Apr 2008
Acute myocardial infarction	Phase 3	MX	Sanofi	01 Apr 2008
Diabetic Coma	Phase 3	US	Sanofi	01 Apr 2008
Diabetic Coma	Phase 3	AR	Sanofi	01 Apr 2008
Diabetic Coma	Phase 3	BR	Sanofi	01 Apr 2008
Diabetic Coma	Phase 3	CA	Sanofi	01 Apr 2008
Diabetic Coma	Phase 3	MX	Sanofi	01 Apr 2008

Clinical Result

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03406000 (TOP1, Pubmed)	Phase 4	Diabetes Mellitus, Type 1	-	Twice-daily basal insulin	fyqxnyqzxa(hgxtnntwts) = ipwxfjbxyz zmnqkodxwg (jnowzelglm ) View more	Positive	09 Jul 2024
NCT01524705 (FLAT-SUGAR, CTgov)	Phase 4	Diabetes Mellitus, Type 2	102	Insulin Glargine+Exenatide+Metformin	xokiebcbzp(uumfrdgdkz) = maapsvahhq ptnpocwoxx (aviruehuxc, guyotyoral - ivpiszkyww) View more	-	29 Dec 2023
EASD2023	Not Applicable	Diabetes Mellitus, Type 2	-	Insulin glargine 300 U/mL (Gla-300)	phxjtmjpgj(xaafgtmyzt) = epvayabnnj ydexrfyvqy (thcljgquaz )	-	05 Oct 2023
				Long-acting basal insulins (BIs)/NPH insulin	phxjtmjpgj(xaafgtmyzt) = mnrnnevplx ydexrfyvqy (thcljgquaz )
ORIGIN (ESC2023)	Not Applicable	Sex hormone-binding globulin (SHBG) \| testosterone	-	Glargine	lhprwjphid(zqsjghodbh) = zqqpawinsn ghoegatijv (ddfvpgcgma )	-	26 Aug 2023
				Glargine	lhprwjphid(zqsjghodbh) = esdrabgnsq ghoegatijv (ddfvpgcgma )
RESTORE-G (ADA2023)	Not Applicable	-	-	Glargine 300 U/mL	slgzoeobjc(duakonxjed) = wmrokfcord vfhpoxkrfi (mgtonkdjfh )	-	23 Jun 2023
ADA2023	Not Applicable	-	-	Bridging dose of G with first dose of D	emkpwagzhi(lkxlmuaaqn) = migixmjgos vfkhthljca (ywkubzxpcb )	-	20 Jun 2023
				Placebo	wmguzafeko(kceosvjqtd) = sdwgtfxxkn eiownxonxz (enrssqdkmv )
GRADE (ASN2022)	Not Applicable	Diabetes Mellitus, Type 2	-	Sitagliptin	tijvkpwjxt(hbahlwrwvb) = hxmbfhjbka ipthlpnkcb (wgqvxccpbb, -2.20 to -1.86)	Negative	03 Nov 2022
				Glimepiride	tijvkpwjxt(hbahlwrwvb) = ctuuuloqqg ipthlpnkcb (wgqvxccpbb, -2.08 to -1.75)
NCT03703869 (ATOS, EASD2022)	Not Applicable	Diabetes Mellitus, Type 2	3,651	insulin glargine 300 U/mL	opncozhufg(zkeblqhsdu) = afetvtzhqv bwdlnyepea (pczcugddbc ) View more	Positive	20 Sep 2022
				insulin glargine 300 U/mL	opncozhufg(zkeblqhsdu) = phokqxhavv bwdlnyepea (pczcugddbc ) View more
NCT04567225 (CTgov)	Phase 4	Diabetic Ketoacidosis \| Diabetes Mellitus, Type 2 \| Diabetes Mellitus, Type 1	39	IV insulin infusion+Early Glargine (Early Glargine)	rdycdqesqt(tcursaqubx) = ycjpflytfi lccmtujhwl (nohupbtrxw, wyjramzgmb - fbdseqqnkz) View more	-	25 Aug 2022
				IV insulin infusion+Late Glargine (Standard Practice (Late Glargine))	rdycdqesqt(tcursaqubx) = ywgmelvjmv lccmtujhwl (nohupbtrxw, mjepshzasz - iolmzbhgpe) View more
ADA2022	Not Applicable	Diabetes Mellitus, Type 2	-	NPH	gfttbyaoaz(eobgalzptb) = yomjcxpily qxexmhhmov (dcnvcyfmkv )	-	01 Jun 2022

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