- Metformin 1000 mg BID
- Lantus® U-100, 30 Units QD
- Humalog® U-100, 7 Units TID
- Lisinopril 20 mg QD
- Atorvastatin 10 mg QD
- A1C: 8.4%
- FPG: 121 mg/dL
- PPG: 210-245 mg/dL
- BMI: 26 kg/m2
- After 10 years, PPG was not controlled on basal insulin alone, so rapid was initiated
- Reliant on caregiver for meals and multiple daily injections due to dexterity limitations
- Missed doses due to confusion of multiple pens and caretaker availability
- After 3 months on one shot of rapid insulin, two additional shots were added to stabilize PPG
- Has been hospitalized due to hypoglycemia
- Recently diagnosed with diabetic retinopathy Struggles to get PPG levels daily History of hypercholesterolemia
- Concerned about co-pays/out-of-pocket costs
- Medicare Advantage Prescription Drug Plan
- Struggles to be available to assist with multiple daily injections
- Due to his own medical needs, sometimes relies on his 50-year-old son to assist with caregiver duties
- Lacks training on treating diabetes
Physical & lab evaluation
In the LixiLan-L Pivotal Trial,
SOLIQUA 100/33 demonstrated ~2x greater A1C reductions vs Lantus®1,2
1.1% mean reduction from baseline for SOLIQUA 100/33 vs 0.6% for Lantus. Consider other antidiabetic therapies in patients with a history of pancreatitis.
The most common adverse events were nausea, nasopharyngitis, headache, diarrhea, vomiting, and upper respiratory tract infection.
Study Design: A randomized, 30-week, open-label, multicenter study of adult patients with T2DM was conducted to evaluate the efficacy and safety of SOLIQUA 100/33 (n=365) or Lantus (n=365). Metformin was continued if previously taken and any other OADs were discontinued. The primary endpoint was change from baseline A1C at Week 30. The maximum allowable insulin glargine dose was 60 Units for both treatment groups. The trial was designed to show the contribution of the GLP-1 RA component to glycemic lowering, and the insulin glargine dose and dosing algorithm were selected in order to isolate the effect of the GLP-1 RA component.
Analysis limitations: The difference in effect observed in the trial may not necessarily reflect the effect that will be observed in the care setting where alternative insulin glargine dosages can be used.
SoliComplex Real-World Observational Analysis
Adults With T2DM Were 2x More Persistent Taking SOLIQUA 100/33 vs Basal-Bolus Insulin3
Reduced Rates of Hypoglycemia Were Observed in Adults With T2DM Taking SOLIQUA 100/33 vs Basal-Bolus Insulin3
Hypoglycemia is the most common adverse event with insulin-containing therapy.1
- Hypoglycemia events were defined by either ICD-10-CM codes or by laboratory results with a blood glucose level <70 mg/dL.3
- Hypothesis-generating and has inherent limitations as it was not prespecified.
- Not powered to determine causal relationships between variables and endpoints; evaluates association only.
- Based on a retrospective chart review, which can have the potential for selection bias.
- Based on a persistency assessment that did not account for titration, hospitalization, or other sources of insulin (e.g., samples) that can cause a delay in filling prescriptions.
- Some data were collected during the COVID-19 pandemic and influence on the results of any endpoints assessed is not known.
aPrimary outcome (statistical analysis was prespecified for the primary outcome [treatment persistence; overall population] only). All other endpoints were secondary.3
bLaboratory defined; using one count per person per day.3
cED visits and hospitalizations.3
dFor inclusion in the A1C analysis participants had to have a valid baseline and a follow-up A1C value at 12 months; therefore, this analysis was conducted in a small proportion of the overall population.3
When A1C Is High, the ADA Recommends the Use of a Basal Insulin Plus a GLP-1 RA to Get A1C Down4
The 2023 ADA Guidelines recommend initial injectable combinations, such as basal insulin plus a GLP-1 RA, when A1C is ≥1.5% above target.
SOLIQUA 100/33 is a combination of a long-acting human insulin analog with a glucagon-like peptide-1 (GLP-1) receptor agonist (RA) indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
Limitations of Use:
- Has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis.
- Not recommended for use in combination with any other product containing a GLP-1 receptor agonist.
- Not for treatment of type 1 diabetes mellitus or diabetic ketoacidosis.
- Not recommended for use in patients with gastroparesis.
- Has not been studied in combination with prandial insulin.
Important Safety Information
Important Safety Information for SOLIQUA 100/33 (insulin glargine and lixisenatide) injection 100 Units/mL and 33 mcg/mL
- During episodes of hypoglycemia.
- In patients with known serious hypersensitivity to insulin glargine, lixisenatide, or to any of the product components.
Warnings and Precautions
- Anaphylaxis and Serious Hypersensitivity Reactions: In clinical trials of lixisenatide, there have been cases of anaphylaxis and other serious hypersensitivity reactions including angioedema. Severe, life-threatening, generalized allergic reactions, including anaphylaxis and angioedema, can occur with insulins, including insulin glargine. There have been reports of serious hypersensitivity reactions, including anaphylactic reactions and angioedema, in patients treated with SOLIQUA 100/33. If hypersensitivity reactions occur, discontinue SOLIQUA 100/33. Use caution in patients with a history of anaphylaxis or angioedema with another GLP-1 RA because it is unknown whether such patients will be predisposed to anaphylaxis.
- Pancreatitis: Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 RAs. Cases of pancreatitis were reported in clinical trials of lixisenatide. After initiation of SOLIQUA 100/33, observe patients for signs and symptoms of pancreatitis (e.g., persistent severe abdominal pain, sometimes radiating to the back and which may be accompanied by vomiting). If pancreatitis is suspected, SOLIQUA 100/33 should promptly be discontinued. If pancreatitis is confirmed, restarting SOLIQUA 100/33 is not recommended and other antidiabetic therapies should be considered.
- Never Share a SOLIQUA 100/33 SoloStar® Pen between Patients: Pen-sharing poses a risk for transmission of blood-borne pathogens, even if the needle is changed.
- Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Changes in insulin regimen including, strength, manufacturer, type, injection site or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Changes should be made cautiously and the frequency of blood glucose monitoring should be increased. Adjustments in concomitant oral antidiabetic treatment may be needed. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis may result in hyperglycemia; sudden change in the injection site (to unaffected area) has been reported to result in hypoglycemia. Advise patients to rotate injection site to unaffected areas and closely monitor for hypoglycemia.
- Medication Errors: SOLIQUA 100/33 contains two drugs. Do not administer more than 60 units of SOLIQUA 100/33, which may result in overdose of the lixisenatide component. Do not use other GLP-1 RAs. Accidental mix-ups between insulin products have been reported. Instruct patients to always check the label before administration. Do not withdraw SOLIQUA 100/33 from the pen with a syringe.
- Hypoglycemia: Hypoglycemia is the most common adverse reaction associated with insulin-containing therapy, which may be life-threatening. Increase frequency of glucose monitoring with changes to: insulin dosage, co-administered glucose lowering medications, meal pattern, physical activity, and in patients with renal or hepatic impairment and hypoglycemia unawareness.
- Acute Kidney Injury: There have been reports of acute renal failure and worsening of chronic failure, which may sometimes require hemodialysis in patients treated with SOLIQUA 100/33. Some of these events were reported in patients without known underlying renal disease. Most reports occurred in patients who experienced nausea, vomiting, diarrhea, or dehydration; advise patients to take precautions to avoid fluid depletion. Monitor blood glucose and renal function in patients with renal impairment. SOLIQUA 100/33 is not recommended in patients with end-stage renal disease.
- Immunogenicity: Patients may develop antibodies to insulin and lixisenatide. If there is worsening glycemic control or failure to achieve targeted glycemic control, significant injection site reactions or allergic reactions, then other antidiabetic therapy should be considered.
- Hypokalemia: All insulin containing products can cause hypokalemia, which may be life-threatening. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk of hypokalemia and treat if indicated.
- Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists: Fluid retention, which may lead to or exacerbate heart failure, can occur with concomitant use of thiazolidinediones (TZDs) and insulin. These patients should be observed for signs and symptoms of heart failure. If heart failure occurs, dosage reduction or discontinuation of TZD must be considered.
- Acute Gallbladder Disease: Acute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in GLP-1 receptor agonist trials and post-marketing. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated.
Most Common Adverse Reactions
The most common adverse reactions reported in ≥ 5% of patients treated with SOLIQUA 100/33 include hypoglycemia, nausea, nasopharyngitis, diarrhea, upper respiratory tract infection, headache
- Certain drugs may affect glucose metabolism, requiring dose adjustment of SOLIQUA 100/33 and close monitoring of blood glucose.
- The signs of hypoglycemia may be reduced or absent in patients taking anti-adrenergic drugs (eg, beta-blockers, clonidine, guanethidine, and reserpine).
- The lixisenatide in SOLIQUA 100/33 delays gastric emptying, which may reduce the rate of absorption of orally administered medication with a narrow therapeutic ratio or that require careful clinical monitoring. If such medications are to be administered with food, do not co-administer with SOLIQUA 100/33.
- Antibiotics, acetaminophen, or other medications that are dependent on threshold concentrations for efficacy, or where a delay in effect is undesirable, should be administered at least 1 hour before SOLIQUA 100/33 injection.
- Oral contraceptives should be taken at least 1 hour before SOLIQUA 100/33 administration or 11 hours after.
Abbreviations: A1C, glycated hemoglobin; BID, twice daily; BMI, body mass index; COVID, coronavirus disease; FPG, fasting plasma glucose; GLP-1, glucagon-like peptide-1; OAD, oral antidiabetic drug; QD, daily; RA, receptor agonist; TID, three times daily; T2DM, type 2 diabetes mellitus.
- SOLIQUA 100/33 Prescribing Information.
- Data on File CSR 12405. Sanofi US.
- Pantalone KM, Heller C, Lajara R, et al. Initiation if iGlarLixi vs basal-bolus insulin in adults with type 2 diabetes advancing from basal insulin therapy: the SoliComplex real-world study. Poster 733-P. Presented at ADA 2022. June 3-7, 2022. New Orleans, LA.
- American Diabetes Association. Standards of care in diabetes-2023. Diabetes Care. 2023;46(suppl1):S1-S292.