Combo Generics vs Individual Components: The Real Cost Difference

When you’re on multiple medications, your doctor might suggest a combo pill-a single tablet with two or more drugs inside. It sounds convenient. Fewer pills to swallow. Easier to remember. But here’s the catch: combo generics aren’t always cheaper than buying the same drugs as separate generic pills. In fact, in many cases, they cost way more.

Why Combo Pills Cost More Than You Think

A 2018 study published in JAMA Internal Medicine looked at 29 branded combination drugs used by Medicare Part D. The researchers found that if patients had taken the same active ingredients as separate generic pills instead of the combo, Medicare would’ve saved $925 million in just one year. That’s not a typo. $925 million. For 29 drugs.

Take Janumet, a combo of sitagliptin and metformin. In 2016, Medicare paid an average of $472 for a 30-day supply. Meanwhile, generic metformin alone? At Walmart’s $4 program, it cost $4. Even if you added the cost of generic sitagliptin (which was available at the time), the total would still be under $50. That’s a 90%+ price difference.

Another example: Kazano (alogliptin + metformin). The combo cost $425 a month. Generic metformin? Less than $10. The other component? Even if it was brand-new and expensive, it wouldn’t push the total past $100. So why pay $425?

The answer lies in how drug pricing works. When a company combines an old, off-patent drug with a new, patented one, they can slap a premium price on the whole thing. The old drug is cheap. The new one is expensive. Together? They become a “high-margin product.” It’s called evergreening-using a combo to extend profits when the original patent expires.

The Math Behind the Markup

You’d think two generic drugs added together would cost less than a combo. And usually, they do. But the industry doesn’t always play by those rules.

IQVIA, a major pharmaceutical data firm, found that branded combo drugs typically cost about 60% of what two separate brand-name drugs would cost. That sounds good-until you realize that generic versions of those same drugs cost 80-85% less than brand names. So if you’re comparing a combo to two generics, you’re not comparing apples to apples. You’re comparing a luxury SUV to two used bicycles.

For example, Entresto (sacubitril/valsartan) is a heart failure combo. The brand-name version costs over $500 a month. Generic valsartan? Around $15. Sacubitril? Still under patent, so it’s expensive-but not $500 expensive. Even if sacubitril costs $300, you’re still paying $200 more than necessary.

This isn’t just a U.S. problem. In Europe, Nexlizet (ezetimibe/bempedoic acid) sells for $12 a day in the U.S. and €5 a day in the EU. Ezetimibe has been generic for years. It costs pennies. But because it’s paired with a newer drug, the combo gets a premium price tag.

When Combo Pills Make Sense

Not all combos are bad. Sometimes, they’re the right choice.

For patients with complex conditions-like type 2 diabetes with high blood pressure or HIV on multiple antivirals-taking one pill instead of three or four can improve adherence. Studies show people are 15-20% more likely to stick to their regimen when they have fewer pills. That matters. Missed doses lead to hospitalizations, which cost way more than the drug itself.

The American College of Cardiology found that for certain heart patients, combo pills improved adherence by 25%. That means fewer emergency visits, fewer complications, and better long-term outcomes. If a combo helps you stay healthy, the extra cost might be worth it.

But here’s the key: only if you can’t get the same result with separate generics. If your doctor prescribes a combo without checking if cheaper alternatives exist, you’re probably overpaying.

What You Can Do

You don’t have to accept the price tag. Here’s how to take control:

• Ask your pharmacist: “Are these drugs available as separate generics?”
• Check prices on GoodRx or SingleCare. Type in each drug individually and compare to the combo.
• Ask your doctor: “Is there a generic alternative for each component?”
• If your insurance denies coverage for the combo, file an appeal. Mention the cost difference and cite the JAMA study.
• Request a “combination drug utilization review” through your pharmacy benefit manager. Many plans have programs to flag overpriced combos.

In Australia, where I live, the Pharmaceutical Benefits Scheme (PBS) already has rules to limit combo pricing. If a generic version of one component exists, the PBS often caps the combo price at the sum of the two generics. The U.S. doesn’t have that protection-and that’s why patients pay more.

How Insurance and Formularies Handle Combos

Most Medicare Part D plans don’t automatically cover combo drugs unless you’ve tried the cheaper options first. In fact, 62% of Part D plans require prior authorization for high-cost combos. That means your doctor has to jump through hoops to get approval.

Pharmacy benefit managers (PBMs) use “carve-outs” to exclude expensive combos from standard formularies. They push prescribers toward separate generics. Some plans even offer incentives-like lower co-pays-for choosing the cheaper option.

But here’s the problem: many doctors don’t know the exact prices. They know the combo is “convenient.” They don’t know that metformin costs $4. Or that amlodipine (a blood pressure drug) is $5 as a generic. So they prescribe the combo without realizing the cost difference.

What’s Changing? New Laws and Trends

The Inflation Reduction Act of 2022 gave Medicare the power to negotiate drug prices for the most expensive medications. That includes some combo drugs. Starting in 2026, Medicare will start negotiating prices for 10 combo drugs annually. That could bring down costs significantly.

The FDA is also pushing to speed up generic approvals. More generic versions of individual components mean more pressure on combo drug prices. If you can get generic amlodipine, generic atorvastatin, and generic metformin-all cheap-why pay $600 for a combo?

Some drugmakers are responding with discount programs. Novartis offers Entresto for $10 a month to eligible Medicare patients. Sounds great-until you realize generic valsartan still costs $15 for the whole month. You’re still paying more than necessary.

Bottom Line: Don’t Assume the Combo Is Cheaper

Combo pills aren’t evil. They’re a tool. But they’re being used to extract billions in unnecessary spending. The data is clear: when both drugs in a combo are available as generics, buying them separately almost always saves money.

If you’re on a combo drug, ask three questions:

1. Are both components available as generics?
2. What’s the total cost of buying them separately?
3. Will my doctor agree to switch if it saves me money?

You’re not being difficult. You’re being smart. And you’re not alone. Millions of people are overpaying because they assume the combo is the default-and the cheapest-option. It’s not. With a little research, you could save hundreds-or even thousands-each year.

What to Do Next

1. Make a list of all your medications. Highlight any combos.

2. Go to GoodRx or your local pharmacy’s price checker. Search each drug individually.

3. Add up the total cost of the separate generics.

4. Compare it to your combo’s copay.

5. If the combo costs more than 2x the sum of the generics, ask your doctor about switching.

It’s not about rejecting convenience. It’s about not paying for convenience you don’t need.