New Soliqua 100/33 data shows improved blood sugar control without weight gain versus premixed insulin

* Study also shows more people on Soliqua 100/33 had improved blood sugar control without weight gain and without low blood sugar events (hypoglycemia) in first head-to-head comparison with premixed insulin

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Sanofi

Jun 28, 2021, 10:00 ET

PARIS, June 28, 2021 /PRNewswire/ -- A new study of Soliqua^® 100/33 (insulin glargine and lixisenatide injection) 100 Units/mL and 33 mcg/mL, iGlarLixi, met its two primary endpoints and all key secondary endpoints in a head-to-head comparison against premixed insulin (biphasic insulin aspart 30, BIAsp 30) in adults living with type 2 diabetes, the most common form of diabetes, uncontrolled on insulin and one or two oral anti-diabetic medicines. The findings were presented today at the American Diabetes Association (ADA) 81^st Scientific Sessions¹ and simultaneously published in Diabetes Care.²

The study met both primary endpoints with Soliqua 100/33 demonstrating noninferiority of blood sugar (HbA_1c) reduction and superiority on body weight change from baseline compared to premixed insulin. The study also met its key secondary endpoints with Soliqua 100/33 achieving a greater proportion of people reaching a HbA_1c target of <7% without weight gain, a greater proportion of people reaching a HbA_1c target of <7% without weight gain and without hypoglycemia, and superiority in reduction of HbA_1c compared with those using premixed insulin.

"Concerns about hypoglycemia and weight gain are known barriers when advancing basal insulin therapy, especially with complex insulin regimens," says Julio Rosenstock, Director of the Dallas Diabetes Research Center at Medical City, Dallas, TX, and main author of the study. "These results show improved outcomes with iGlarLixi over BIAsp 30, demonstrating better glucose control without body weight gain and less hypoglycemia. This combined benefit could help clinicians consider advancing basal insulin therapy by switching to a once-daily fixed-ratio combination of basal insulin plus a GLP-1 receptor agonist rather than switching to a twice-daily premixed insulin regimen."

A secondary analysis also found study participants using Soliqua 100/33 reported greater improvements in patient-reported outcomes compared to premixed insulin as measured by Treatment-Related Impact Measure Diabetes (TRIM-D) and patient- and physician-rated Global Treatment Effectiveness Evaluation (GTEE) scores.³ These tools include measurements of treatment burden, daily life, diabetes management, compliance, psychological health, and treatment effectiveness.

"Despite the advances in diabetes care, many people living with type 2 diabetes are unable to reach their HbA1c goals," said Luigi Meneghini, M.D., US Medical Head of Diabetes, General Medicines at Sanofi. "This study highlights appropriate options for earlier treatment intensification for those not reaching their blood sugar goals, and these data suggest that Soliqua 100/33 may be a superior therapy for these people compared to premixed insulins."

Safety findings were in line with the established profiles of Soliqua 100/33 and premixed insulin.

About the SoliMix study

The SoliMix study was a 26-week, randomized controlled trial of 887 adults living with type 2 diabetes who were uncontrolled on insulin plus metformin with or without a sodium-glucose cotransporter-2 inhibitor (SGLT-2i). The study compared the efficacy and safety of Soliqua 100/33 compared to a commonly used premixed insulin (BIAsp 30). Participants were randomized to switch from their prior insulin to either Soliqua 100/33 once daily or premixed insulin twice daily, with starting doses determined and adjusted weekly. Any metformin or SGLT-2i treatment was maintained through the study period.

The study met its two primary endpoints and all three of its key secondary endpoints.

SoliMix Data Summary
		Soliqua 100/33 (n=443)	Premixed Insulin (n=444)
HbA1c, %	Baseline	8.61 ± 0.67	8.57 ± 0.65
	LS mean change from baseline to Week 26 ± SE	-1.30 ± 0.06	-1.05 ± 0.06
	LS mean difference (97.5% CI)* p-value for non-inferiority† LS mean difference (95% CI)‡ p-value for superiority§	-0.24 (-0.41, -0.08) p<0.001 -0.24 (-0.39, -0.10) p<0.001
HbA1c, mmol/mol	Baseline	70.6 ± 7.3	70.2 ± 7.1
	LS mean change from baseline to Week 26 ± SE	-14.2 ± 0.7	-11.5 ± 0.7
	LS mean difference (97.5% CI)* p-value for non-inferiority† LS mean difference (95% CI)‡ p-value for superiority§	-2.6 (-4.5, -0.9) p<0.001 -2.6 (-4.3, -1.1) p<0.001
Bodyweight, kg	Baseline	80.7 ± 16.5	82.2 ± 18.5
	LS mean change from baseline to Week 26 ± SE	-0.70 ± 0.20	+1.15 ± 0.20
	LS mean difference (95% CI) p-value for superiority*	-1.86 (-2.28, -1.43) p<0.001
HbA1c <7 % without weight gain, n (%) Odds ratio (95% CI)‡		122 (27.5)		55 (12.4)
		2.83 (1.98, 4.04); p<0.001
HbA1c <7 % without weight gain and without hypoglycemia (plasma glucose <70 mg/dL [<3.9 mmol/L]), n (%) Odds ratio (95% CI)‡		86 (19.4)		31 (7.0)
		3.40 (2.19, 5.28); p<0.001
HbA1c <7 %, n (%)§ Odds ratio (95% CI)		187 (42.2)		141 (31.8)
		1.65 (1.25, 2.19)
Incidence and rates of hypoglycemia (safety population)		n=442 223.15 PY	n=441 217.85 PY
Level 1 (ADA definition: <70 mg/dL [<3.9 mmol/L] and ≥54 mg/dL [≥3.0 mmol/L])
n (%) Odds ratio (95% CI) PPY (events) Rate ratio (95% CI)		114 (25.8)	170 (38.5)
		0.55 (0.42, 0.74)
		2.03 (453)	2.83 (616)
		0.71 (0.52, 0.99)
Level 2 (ADA definition: <54 mg/dL [<3.0 mmol/L])
n (%) Odds ratio (95% CI) PPY (events) Rate ratio (95% CI)		28 (6.3)	57 (12.9)
		0.45 (0.28, 0.73)
		0.25 (56)	0.56 (121)
		0.40 (0.23, 0.71)
Level 3 (ADA definition: severe hypoglycemia)¶
n (%) Odds ratio (95% CI) PPY (events) Rate ratio (95% CI)		1 (0.2)	2 (0.5)
		0.50 (0.04, 5.56)
		0 (1)	0.01 (2)
		0.49 (0.04, 5.40)
Data shown are mean ± SD unless otherwise specified. *Primary endpoint was assessed at 0.025 for non-inferiority on HbA1c change from baseline then 0.05 for other endpoints, as the alpha was distributed to subsequent tests. †Two primary efficacy endpoints, non-inferiority of HbA1c reduction assessed using a margin of 0.3 %; ‡Secondary endpoint was assessed at the alpha 0.05 level. §Secondary endpoint. ¶A hypoglycemic event with severe cognitive impairment (hypoglycemic unconsciousness) requiring external assistance for recovery. ADA, American Diabetes Association; AE, adverse event; BiAsp, biphasic aspart insulin; BMI, body mass index; CI, confidence interval; iGlarLixi, a fixed-ratio combination of insulin glargine 100 U/mL and the glucagon-like peptide-1 receptor agonist, lixisenatide; ITT, intent to treat population; LS, least squares; PPY, per participant-year; PY, participant-year; SD, standard deviation; SE, standard error; T2D, type 2 diabetes.

In a secondary analysis, participants using Soliqua 100/33 also reported greater improvements in patient-reported outcomes as measured by TRIM-D and patient- and physician-rated GTEE scores at 26 weeks.

TRIM-D results demonstrated greater improvements for participants using Soliqua 100/33 compared to those using premixed insulin, across domains including compliance, diabetes management, and psychological health, among others.³
GTEE findings showed that nearly twice as many patients reported complete control of their diabetes with Soliqua 100/33 compared to premixed insulin (27.5% vs 15%). Similarly, nearly twice as many physicians also reported treatment effectiveness (i.e., complete control of diabetes) with Soliqua 100/33 compared to premixed insulin (29.9% vs 15.3%).³

Safety findings were in line with the established profiles of both treatments. The most commonly reported adverse events in the study were hypoglycemia (31.2% Soliqua 100/33, 42.4% premixed insulin), nausea (7.7% Soliqua 100/33, 0% premixed insulin), headache (2.5% Soliqua 100/33, 0.5% premixed insulin), dizziness (1.4% Soliqua 100/33, 0.5% premixed insulin), and vomiting (1.1% Soliqua 100/33, 0.2% premixed insulin).

About Soliqua 100/33

Soliqua 100/33 is an injectable prescription medicine that contains 2 diabetes medicines, insulin glargine and lixisenatide, which may improve blood sugar (glucose) control in adults with type 2 diabetes when used with diet and exercise.

It has not been studied in people with a history of pancreatitis.
It is not recommended for people who also take lixisenatide or other medicines called GLP-1 receptor agonists.
It is not for use in people with type 1 diabetes, or people with diabetic ketoacidosis.
It has not been studied in people who have a stomach problem that causes slow emptying (gastroparesis) and is not for people with slow emptying of the stomach.
It has not been studied in people who also take a short-acting (prandial) insulin.
It is not known if Soliqua 100/33 is safe and effective in children under 18 years of age.

Important Safety Information

What is the most important information I should know about Soliqua 100/33?

Do not share your Soliqua 100/33 pen with other people, even if the needle has been changed. You may give other people a serious infection, or get a serious infection from them.

Soliqua 100/33 can cause serious side effects, including inflammation of the pancreas, which may be severe and lead to death.

Before using Soliqua 100/33, tell your doctor if you have had pancreatitis, stones in your gallbladder (cholelithiasis), or a history of alcoholism. These medical problems may make you more likely to get pancreatitis.

Stop taking Soliqua 100/33 and call your healthcare provider right away if you have pain in your stomach area (abdomen) that is severe, and will not go away. The pain may be felt in the back area. The pain may happen with or without vomiting.

Who should not use Soliqua 100/33?

Do not use Soliqua 100/33 if you:

are having an episode of low blood sugar (hypoglycemia)
are allergic to insulin glargine, lixisenatide, or any of the ingredients in Soliqua 100/33. Symptoms of a severe allergic reaction with Soliqua 100/33 may include swelling of the face, lips, tongue, or throat, fainting or feeling dizzy, problems breathing or swallowing, very rapid heartbeat, severe rash or itching, or low blood pressure.

Before using Soliqua 100/33, tell your healthcare provider about all your medical conditions, including if you:

have or have had problems with your pancreas, your kidneys, or your liver, stones in your gallbladder, or a history of alcoholism.
have heart failure or other heart problems. If you have heart failure, it may get worse while you take thiazolidinediones (TZDs).
have severe problems with your stomach, such as slowed emptying of your stomach or problems digesting food.
are taking certain medicines called glucagon-like peptide 1 receptor agonists (GLP-1 receptor agonists).
have had an allergic reaction to a GLP-1 receptor agonist.
are pregnant or breastfeeding or plan to become pregnant or to breastfeed. It is not known if Soliqua 100/33 will harm your unborn baby or pass into your breast milk.

Tell your healthcare provider about all the medicines you take, including all prescription and over-the-counter medicines, vitamins, and herbal supplements. Soliqua 100/33 may affect the way some medicines work. Before using Soliqua 100/33, talk to your healthcare provider about low blood sugar and how to manage it.

How should I use Soliqua 100/33?

Do not change your dose without first talking to your healthcare provider.
Check the pen label each time you inject to make sure you are using the correct medicine.
Do not take more than 60 units of Soliqua 100/33 each day. Do not take Soliqua 100/33 with other GLP-1 receptor agonists.
Only use Soliqua 100/33 that is clear and colorless to almost colorless. If you see small particles, return it to your pharmacy for replacement.
Do not remove Soliqua 100/33 from the pen with a syringe.
Do not re-use or share needles with other people. You may give other people a serious infection, or get a serious infection from them.
Check your blood sugar levels. Ask your healthcare provider what your blood sugar should be and when you should check.

What are the possible side effects of Soliqua 100/33?
Soliqua 100/33 may cause serious side effects, including:

Serious allergic reactions. Stop taking Soliqua 100/33 and get help right away if you have any symptoms of a serious allergic reaction, including swelling of your face, lips, tongue, or throat, problems breathing or swallowing, severe rash or itching, fainting or feeling dizzy, and very rapid heartbeat.
Low blood sugar (hypoglycemia). Your risk for getting low blood sugar is higher if you take another medicine that can cause low blood sugar. Signs and symptoms of low blood sugar may include headache, dizziness, drowsiness, sweating, weakness, irritability, hunger, blurred vision, fast heartbeat, feeling jittery, confusion, and anxiety.
Kidney problems (kidney failure). In people who have kidney problems, diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration), which may worsen kidney problems.
Low potassium in your blood (hypokalemia).
Heart failure. Taking certain diabetes pills called TZDs (thiazolidinediones) with Soliqua 100/33 may cause heart failure in some people. This can happen even if you have never had heart failure or heart problems before. If you already have heart failure, it may get worse while you take TZDs with Soliqua 100/33. Tell your healthcare provider if you have any new or worse symptoms of heart failure, including shortness of breath, swelling of your ankles or feet, or sudden weight gain. Treatment with TZDs and Soliqua 100/33 may need to be adjusted or stopped if you have new or worse heart failure.

The most common side effects of Soliqua 100/33 include low blood sugar (hypoglycemia), nausea, diarrhea, upper respiratory infection, stuffy or runny nose, and headache. Nausea and diarrhea usually happen more often when you first start using Soliqua 100/33.

Click here for full Prescribing Information for Soliqua 100/33.

References

Rosenstock, J., et al. "Advancing Therapy in Uncontrolled Basal Insulin-Treated Type 2 Diabetes (T2D): Better Clinical Outcomes with iGlarLixi vs Premix 70/30 in the SoliMix Trial", Presentation 234-OR, American Diabetes Association (ADA) 81^st Scientific Sessions (virtual event), June 28, 2021.
Rosenstock, J., et al. Advancing therapy in suboptimally controlled basal insulin-treated type 2 diabetes: Clinical outcomes with iGlarLixi versus premix BIAsp 30 in the SoliMix randomized controlled trial. Diabetes Care. 2021 Jun 28.
Polonsky, W., et al. "Improved Treatment Perceptions with iGlarLixi vs Premix Insulin in Type 2 Diabetes (T2D) Uncontrolled on Basal Insulin (BI) + Oral Antihyperglycemic Drugs (OADs): Patient-reported Outcomes (PROs) of the SoliMix Trial", Presentation 747-P, American Diabetes Association (ADA) 81^st Scientific Sessions (virtual event), June 28, 2021.

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