Last update 01 Nov 2024

Diabetes Mellitus, Lipoatrophic

Last update 01 Nov 2024

Basic Info

Synonyms

DIABETES, LIPOATROPHIC, Diabete, Lipoatrophic, Diabetes Mellitus, Lipoatrophic

+ [20]

Introduction

A type of diabetes mellitus that is characterized by severe INSULIN RESISTANCE and LIPODYSTROPHY. The latter may be generalized, partial, acquired, or congenital (LIPODYSTROPHY, CONGENITAL GENERALIZED).

Drugs associated with Diabetes Mellitus, Lipoatrophic

Empagliflozin

Target

SGLT2

Mechanism

SGLT2 inhibitors

Active Org.

Eli Lilly & Co. [+10]

Originator Org.

Boehringer Ingelheim GmbH

Active Indication

Cardiovascular Diseases [+19]

Inactive Indication

Acute decompensated heart failure [+17]

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

First Approval Date30 Apr 2014

Mecasermin

Target

IGF-1R

Mechanism

IGF-1R agonists

Active Org.

Orphan Pharma International

Originator Org.

Astellas Pharma, Inc.

Active Indication

Diabetes Mellitus, Lipoatrophic [+3]

Inactive Indication-

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

First Approval Date05 Oct 1994

Clinical Trials associated with Diabetes Mellitus, Lipoatrophic

JPRN-UMIN000043693 / Completed

Patient Experiences and Perceptions of Living with Refractory Diabetes Mellitus with Insulin Resistance in Japan -A Qualitative Research - Refractory Diabetes Mellitus with Insulin Resistance -Patient Experiences and Perceptions in Japan

Start Date23 Mar 2021

Sponsor / Collaborator

Nippon Boehringer Ingelheim Co., Ltd.

NCT04221152 / Unknown statusPhase 3

A Multicenter, Open-label, Single-arm, Extension Study With Regard to the Safety and Efficacy of Empagliflozin in Patients With Refractory Diabetes Mellitus With Insulin Resistance (EMPIRE-02)

A multicenter, open-label, single-arm, extension study with regard to the safety and efficacy of empagliflozin in patients with refractory diabetes mellitus with insulin resistance.

Start Date01 Feb 2020

Sponsor / Collaborator

Kobe University

[+1]

NCT04018365 / Unknown statusPhase 3

A Multicenter, Open-label, Single-arm Study With Regard to the Efficacy and Safety of Empagliflozin in Patients With Refractory Diabetes Mellitus With Insulin Resistance

A multicenter, open-label, single-arm study with regard to the efficacy and safety of empagliflozin in patients with refractory diabetes mellitus with insulin resistance

Start Date01 Sep 2019

Sponsor / Collaborator

Kobe University

[+1]

100 Clinical Results associated with Diabetes Mellitus, Lipoatrophic

100 Translational Medicine associated with Diabetes Mellitus, Lipoatrophic

0 Patents (Medical) associated with Diabetes Mellitus, Lipoatrophic

256

Literatures (Medical) associated with Diabetes Mellitus, Lipoatrophic

01 Sep 2024·Gene Therapy

Preclinical evaluation of tissue-selective gene therapies for congenital generalised lipodystrophy

Article

Author: Roumane, Ahlima ; Mcilroy, George D ; Rochford, Justin J ; Tiwari, Mansi ; Han, Weiping ; Delibegović, Mirela ; Sommer, Nadine

AbstractLipodystrophy is a rare disorder which can be life-threatening. Here individuals fail to develop or maintain appropriate adipose tissue stores. This typically causes severe metabolic complications, including hepatic steatosis and lipoatrophic diabetes. There is no cure for lipodystrophy, and treatment options remain very limited. Here we evaluate whether tissue-selective adeno-associated virus (AAV) vectors can provide a targeted form of gene therapy for lipodystrophy, using a preclinical lipodystrophic mouse model of Bscl2 deficiency. We designed AAV vectors containing the mini/aP2 or thyroxine-binding globulin promoter to selectively target adipose or liver respectively. The AAV-aP2 vectors also contained the liver-specific microRNA-122 target sequence, restricting hepatic transgene expression. Systemic delivery of AAV-aP2 vectors overexpressing human BSCL2 restored adipose tissue development and metabolic health in lipodystrophic mice without detectable expression in the liver. High doses (1 × 1012 GCs) of liver-selective vectors led to off target expression and adipose tissue development, whilst low doses (1 × 1010 GCs) expressed selectively and robustly in the liver but did not improve metabolic health. This reveals that adipose tissue-selective, but not liver directed, AAV-mediated gene therapy is sufficient to substantially recover metabolic health in generalised lipodystrophy. This provides an exciting potential new avenue for an effective, targeted, and thereby safer therapeutic intervention.

01 Sep 2024·Journal of Diabetes Investigation

A multicenter, open‐label, single‐arm trial of the long‐term safety of empagliflozin treatment for refractory diabetes mellitus with insulin resistance (EMPIRE‐02)

Article

Author: Suzuki, Junichi ; Kakei, Yasumasa ; Wada, Jun ; Ogawa, Wataru ; Omori, Takashi ; Ebihara, Ken ; Urakami, Tatsuhiko ; Hirota, Yushi ; Katagiri, Hideki ; Imai, Junta

ABSTRACTAims/IntroductionInsulin resistance syndrome and lipoatrophic diabetes are rare conditions characterized by the development of treatment‐refractory diabetes with severe insulin resistance. We recently conducted a 24 week, multicenter, single‐arm trial (EMPIRE‐01) that demonstrated a certain level of effectiveness and safety of empagliflozin for these conditions. To evaluate treatment safety over a longer period, we have now performed an additional 28 week trial (EMPIRE‐02) that followed on from EMPIRE‐01.Materials and MethodsThe primary and secondary outcomes were safety and efficacy evaluations, respectively. All eight subjects of the EMPIRE‐01 trial participated in EMPIRE‐02.ResultsTwenty adverse events (AEs) were recorded among five individuals during the combined 52 week treatment period of both trials. Whereas one case of chronic hepatitis B was moderate in severity, all other AEs were mild. There were thus no serious AEs or events necessitating discontinuation or suspension of treatment or a reduction in drug dose. Whereas ketoacidosis or marked increases in serum ketone body levels were not observed, the mean body mass of the subjects was decreased slightly after completion of EMPIRE‐02. The improvement in mean values of glycemic parameters observed in EMPIRE‐01 was not sustained in EMPIRE‐02, mostly because of one individual whose parameters deteriorated markedly, likely as a result of nonadherence to diet therapy. The improvement in glycemic parameters was sustained during EMPIRE‐02 after exclusion of this subject from analysis.ConclusionsEmpagliflozin demonstrated a certain level of safety and efficacy for the treatment of insulin resistance syndrome and lipoatrophic diabetes over 52 weeks, confirming its potential as a therapeutic option.

01 Aug 2024·Diabetes, Obesity and Metabolism

Empagliflozin mitigates metabolic dysfunction‐associated steatotic liver disease by reducing de novo lipogenesis in a mouse model of lipoatrophic diabetes

Letter

Author: Deniel, Perrine ; Le May, Cédric ; Cariou, Bertrand ; Sotin, Thibaud ; Smati, Sarra ; Joubert, Michael ; Ducheix, Simon ; Arnaud, Lucie ; Hadjadj, Samy ; Prieur, Xavier

As a first preventive approach, we sought to assess whether empagliflozin could alter the development of hepatic steatosis in SKO mice.Eight-week-old SKO mice and their littermates wild-type (WT) mice were fed either an empagliflozin-supplemented diet (100 mg/kg) or a control diet for 8 wk.The liver mass was increased by four-fold in 16-wk-old SKO mice as compared with WT mice, and empagliflozin treatment reduced liver mass (35%), triglyceride (TG) content (50%) and Oil Red O staining (Figure 1A-C).Consistently, the mRNA levels of the lipid dropletassocd. protein Adrp, a marker of liver steatosis, were increased by three-fold in SKO mice compared with WT mice but were reduced by empagliflozin (Figure 1D).To understand further how empagliflozin limited liver steatosis development in SKO mice, we measured the mRNA levels of three main actors of de novo lipogenesis: Acly, Acc and Fas.MRNA levels of peroxisome proliferator-activated receptor alpha target genes involved in fatty acid utilization, such as Cpt1, Acot2 and Pdk4, were increased in SKO mice, empagliflozin had no addnl. effect (Figure 1J-L).Empagliflozin reduced glycemia (Figure S2C) without altering insulinemia or insulin sensitivity (Figure S2D,E). Empagliflozin treatment reduced liver mass by 19% and liver TG by 26% (Figure 2A-C).The empagliflozin significantly reduced mRNA levels of Adrp but not Mcp1 or Col1a1, suggesting a primary action on liver steatosis rather than on inflammation or fibrosis.Overall, these data showed that empagliflozin was able to improve established liver steatosis in older SKO mice and that this was still associated with a decrease in lipogenic gene expression.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

Diabetes Mellitus, Lipoatrophic

Basic Info

Related

Analysis