Delving into the Latest Updates on Ipragliflozin L-Proline with Synapse

Sodium‒glucose cotransporter 2 (SGLT2) inhibitors have become viable therapeutic options for treating breast cancer. Diabetes is the primary source of these medications. This research examines how SGLT2 blockers can induce apoptosis, decrease the amount of glucose taken up by cancer cells, and modify key signaling pathways, such as the PI3K/AKT/mTOR and MAPK pathways. The effects of four different SGLT2 inhibitors on breast cancer cells were investigated in this study via both in vitro and in vivo testing: dapagliflozin, ipragliflozin, canagliflozin, and empagliflozin. The potential synergistic effects of these inhibitors with conventional chemotherapy medications were also examined. This review explores the complex relationship between SGLT2 inhibitors and breast cancer, examining how drugs interact with this disease at various stages of its development. Additionally, this study highlights how SGLT2 inhibitors may be used in conjunction with precision medicine techniques to treat breast cancer. Although encouraging outcomes have been noted, this review highlights the necessity of additional clinical studies to evaluate the safety and effectiveness of SGLT2 blockers in patients with breast cancer, in addition to ongoing research into the molecular mechanisms underlying the anticancer effects of these drugs.

01 Sep 2025·Annals of Medicine and Surgery

Comparative efficacy of sodium-glucose transporter 2 inhibitors on lipid profiles in nonalcoholic fatty liver disease (NAFLD): a comprehensive Bayesian network meta-analysis

Article

Author: Khalil, Ibrahim ; Al-Badri, Sajjad Ghanim ; Hossain, Md. Imran ; Akter, Mahmuda

Background::

Nonalcoholic fatty liver disease (NAFLD) is a global health concern associated with dyslipidemia, obesity, and type 2 diabetes mellitus (T2DM), necessitating effective therapeutic strategies. Sodium-glucose transporter 2 (SGLT-2) inhibitors have shown promise in improving metabolic parameters, but their comparative efficacy in NAFLD remains unclear.

Methods::

We systematically searched PubMed, Cochrane Library, Scopus, and Embase for randomized controlled trials (RCTs) up to 31 December 2024, involving NAFLD patients treated with SGLT-2 inhibitors versus placebo or standard treatments. Outcomes included changes in low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol, triglycerides, BMI, and HbA1c. A Bayesian NMA was performed using a random-effects model, with mean differences (MD) and 95% credible intervals (CrI) reported. Treatments were ranked using Surface Under the Cumulative Ranking Curve (SUCRA) scores.

Results::

We evaluated and compared the efficacy of SGLT-2 inhibitors in improving lipid profiles (LDL-C, HDL-C, total cholesterol, and triglycerides), BMI, and HbA1c in patients with NAFLD. Eleven RCTs involving 805 patients were included. Empagliflozin achieved the greatest LDL-C reduction (MD: −8.07 mg/dL, 95% CrI: −25.92 to 1.41; SUCRA: 95.38%), total cholesterol reduction (MD: −15.08 mg/dL, 95% CrI: −58.87 to 5.38; SUCRA: 94.32%), and HbA1c reduction (MD: −0.69%, 95% CrI: −1.52 to −0.06; SUCRA: 81.84%). Ipragliflozin non-significantly increased HDL-C (MD: 2.28 mg/dL, 95% CrI: −1.21 to 4.83; SUCRA: 85.11%) and significantly reduced triglyceride (MD: −22.39 mg/dL, 95% CrI: −39.25 to −7.27; SUCRA: 82.26%). Dapagliflozin resulted in significant BMI reduction (MD: −1.23 kg/m2, 95% CrI: −2.11 to −0.41; SUCRA: 73.28%).

Conclusion::

Empagliflozin and ipragliflozin demonstrated superior efficacy in improving lipid profiles, while dapagliflozin was most effective for BMI reduction in NAFLD patients. These findings align with their cardiovascular and metabolic benefits, offering a multifaceted approach to a complex disease. Further research is needed to confirm long-term effects and optimize treatment strategies for diverse NAFLD populations.

01 Jul 2025·DIABETIC MEDICINE

Effect of the SGLT2 inhibitor ipragliflozin on the expression of genes that regulate skin function

Article

Author: Ikarashi, Nobutomo ; Shinozaki, Yui ; Tabata, Keito ; Sakai, Hiroyasu ; Kon, Risako ; Hosoe, Tomoo

Abstract:

Aims:

Skin disorders occur more frequently with sodium‐dependent glucose cotransporter type 2 (SGLT2) inhibitors than with other antidiabetic drugs. We conducted basic research using ipragliflozin, with the aim of identifying new measures to prevent skin disorders caused by SGLT2 inhibitors.

Methods:

db/db type 2 diabetes model mice were orally administered ipragliflozin (10 mg/kg or 30 mg/kg) once a day for 28 days and skin function genes were analysed by real‐time RT‐PCR or Western blotting.

Results:

No difference in the expression level of collagen (Col1a1 and Col1a2) in the skin was detected between the ipragliflozin treatment group and the control group. On the other hand, the expression levels of enzymes involved in the synthesis and decomposition of hyaluronic acid (Has2 and Hayl1) and enzymes involved in the synthesis and decomposition of ceramide (Sptlc1, Sptlc2, Asah1, and Acer1) were significantly decreased by the administration of ipragliflozin. Furthermore, the expression levels of filaggrin (Flg), loricrin (Lor), elastin (Eln), and aquaporin‐3 (Aqp3) in the skin were lower in the ipragliflozin treatment group than in the control group.

Conclusions:

It was revealed that ipragliflozin reduces the expression of genes involved in skin barrier and moisturizing functions, which this may be one of the mechanisms through which this drug causes skin disorders.

100 Deals associated with Ipragliflozin L-Proline

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External Link

KEGG	Wiki	ATC	Drug Bank
D10200	Ipragliflozin L-Proline	A10BK05	DB11698

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Diabetes Mellitus, Type 1	Japan	-	17 Jan 2014
Diabetes Mellitus, Type 2	Japan	-	17 Jan 2014

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hepatic Insufficiency	Phase 1	United States	Astellas Pharma, Inc.	01 May 2010

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


JPRN-UMIN000015170 (EASD2022)	Not Applicable	HbA1c \| BMI \| visceral fat area ... View more	103	Ipragliflozin 50 mg	pcumzzrsxo(rygbrexmlp) = slhbkkuqyt ybyolddqxk (yoztuzbyor )	Positive	20 Sep 2022
				Metformin 1000 mg	pcumzzrsxo(rygbrexmlp) = idwxiyxgza ybyolddqxk (yoztuzbyor )
NCT02479399 (STELLA-LONG TERM, Pubmed \| Diabetol Int)	Not Applicable	Diabetes Mellitus, Type 2 First line	11,412	ipragliflozin (Treatment-naïve patients)	xildkcptcy(uhchuxqtyp) = gevxrzarjf fzmdsogkaw (jflkygrptk ) View more	-	01 Oct 2021
				ipragliflozin (Non-naïve patients)	xildkcptcy(uhchuxqtyp) = ldipotsxkw fzmdsogkaw (jflkygrptk ) View more
NCT02577003 \| NCT02564211 (Pubmed \| Diabetes Obes Metab)	Phase 3	Diabetes Mellitus, Type 2	-	Ipragliflozin 50 mg	qsagshufgs(mcezfkwlvs) = wtafqgsnjy zeupeqbfvz (evvehuevgk )	-	25 May 2021
NCT02479399 (STELLA-LONG TERM, Pubmed \| Diabetes Ther)	Not Applicable	Diabetes Mellitus, Type 2	11,412	Ipragliflozin in patients aged <65 years	iatpyyurwr(zuyyvhdanr) = hbfivgfsfa fbojnbcujd (uuiicrlepy ) View more	-	17 Mar 2021
				Ipragliflozin in patients aged ≥65 years	iatpyyurwr(zuyyvhdanr) = enlwpgfamy fbojnbcujd (uuiicrlepy ) View more
JPRN-jRCTs031180205 (ADA2020)	Phase 4	Diabetes Mellitus, Type 2 Second line	-	Ipragliflozin	lmjdbhokui(aoyjnuuoeh) = xwegthzimg cozpmcnhwd (mmmhxjgbzp ) View more	-	01 Jun 2020
				Sitagliptin	lmjdbhokui(aoyjnuuoeh) = pofsjfqrmq cozpmcnhwd (mmmhxjgbzp ) View more
NCT01225081 \| NCT01071850 \| NCT01117584 \| NCT00621868 \| NCT01057628 \| NCT01135433 \| NCT01316094 \| NCT02452632 \| NCT02175784 \| NCT01242215 \| NCT01505426 \| NCT02794792 (Pubmed \| Diabetes Ther)	Not Applicable	Diabetes Mellitus, Type 2	-	Ipragliflozin 50 mg	ojzqtxqywk(objnxqyabq) = agiucawccc fipngbiaem (lxnnxjwwra ) View more	-	01 Dec 2019
				Placebo	ojzqtxqywk(objnxqyabq) = fljrnwokjf fipngbiaem (lxnnxjwwra ) View more
NCT02479399 (STELLA-LONG TERM, Pubmed \| Curr Med Res Opin)	Not Applicable	Diabetes Mellitus, Type 2	11,412	ipragliflozin (Non-elderly patients)	ekvslyrtlo(kkowxjdpnx) = ynahkayidf czltnxfmpv (ncoivunkmz ) View more	-	01 Nov 2019
				ipragliflozin (Elderly patients)	ekvslyrtlo(kkowxjdpnx) = tppjbogqjs czltnxfmpv (ncoivunkmz ) View more
NCT02897219 (Pubmed) Manual	Phase 3	Diabetes Mellitus, Type 1	175	insulin+ipragliflozin	pfjetlexjg(krcppmzrmd): difference = -3.8 (95% CI, -6.2 to -1.5) View more	Positive	01 Oct 2019
				insulin+Placebo
JPRN-UMIN000015170 (EASD2019)	Not Applicable	insulin \| α1microglobulin (α1MG) \| glutamic pyruvic transaminase (GPT)	103	Ipragliflozin	mlcpeqlmht(prtjpayxdq) = xqwubklalk bydlnjuowe (rhkwtgspcl ) View more	Positive	17 Sep 2019
				Metformin	mlcpeqlmht(prtjpayxdq) = whncyutebq bydlnjuowe (rhkwtgspcl ) View more
JPRN-UMIN000015170 (EASD2018)	Not Applicable	Diabetes Mellitus, Type 2 First line visceral fat area \| bone-specific alkaline phosphatase (BAP) \| tartrate-resistant acid phosphatase-5b (TRACP-5b)	103	Ipragliflozin 50 mg/day	eewhrefini(yixabujppg) = wrlhciledj okncaxyjmg (wgkdzdaioh ) View more	Negative	05 Oct 2018
				Metformin 1000-1500 mg/day	eewhrefini(yixabujppg) = jrbzywlwtm okncaxyjmg (wgkdzdaioh ) View more