Aetna Inc. is nearing a deal to buy Humana Inc., according to people familiar with the matter, in a tie-up of health insurers that could be announced this week.

The people said a deal could be inked as soon as Thursday night, though they cautioned the timing could slip.

With Humana's market value at $28.9 billion as of Thursday's market close, a takeover of the Louisville, Ky. insurer would mark the latest megamerger in a year on track to reach historic M&A volumes.

A takeover approach for Humana earlier this year thrust the biggest health-insurance companies into a five-way merger frenzy. Cigna Corp. and Aetna were vying to buy Humana, while trying to rebuff takeover approaches of their own. Cigna has been in talks with Anthem Inc., and UnitedHealth Group Inc. earlier approached Aetna.

A deal to buy Humana would vault Aetna toward the top of the burgeoning Medicare business and give it scale to thrive as the industry consolidates.

But expected scrutiny from antitrust regulators, along with signs of some emerging operational challenges at Humana, will put pressure on Aetna and its chief executive, Mark Bertolini, to demonstrate that the big bet will pay off.

In picking up Humana, Aetna would get a unique asset—a company with a rapidly growing Medicare enrollment that totals 3.2 million. This, combined with Aetna's Medicare membership of 1.26 million, would likely put the merged company close to current industry leader UnitedHealth.

The Medicare business is considered a growth engine for the industry, as baby boomers age into eligibility and choose the private-insurer version of the government program, known as Medicare Advantage plans.

Humana performs strongly in a key measure of Medicare quality known as star ratings, which are tied to government payments. The insurer has been moving rapidly to forge close ties with doctors and other providers in efforts to boost performance and rein in costs.

Humana is also a leading provider of Medicare drug benefits, known as Part D plans, with 18% of that market, according to a tally by Wells Fargo Securities.

A deal would have particularly high stakes for the federal government because of Humana's key role in Medicare and its significant footprint in the health law's insurance exchanges.

A Wall Street Journal analysis found that an Aetna-Humana tie-up would increase by about 180 the number of U.S. counties where at least 75% of customers for Medicare Advantage plans are in the hands of a single insurer. In eight states, an Aetna-Humana merger would remove a competitor from the exchanges in which individuals can buy coverage under the Affordable Care Act, though insurers may not offer plans in every region of a state.

Goldman Sachs health-insurance analysts, looking at potential market-concentration issues, estimated that around 13% of the combined Medicare Advantage enrollment of a combined Aetna-Humana could be at risk of divestiture if the two companies sought to merge. The analysts estimated the figure at around 18% of the combined individual-insurance business and 16% of small-group plan enrollment, though some states were excluded from those tallies.

Write to Liz Hoffman at liz.hoffman@wsj.com and Dana Mattioli at dana.mattioli@wsj.com

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