By Dana Mattioli, Anna Wilde Mathews 

Anthem Inc. agreed to buy Cigna Corp. for $48 billion, capping months of merger frenzy among top U.S. health insurers that could result in a dramatic reshaping of the industry.

The deal, combining the second- and fifth-largest health insurers by revenue, would create a company with a huge footprint in commercial insurance, the type of coverage provided to employers and consumers.

The merged company is projected to have around $115 billion in annual revenue and cover about 53.2 million people. The impending deal and its price was first reported by The Wall Street Journal earlier this week.

The tie-up of Anthem and Cigna follows by about three weeks Aetna Inc.'s agreement to buy Humana Inc. for $34 billion and further accelerates the rapid-fire reconfiguration of the U.S. health-insurance industry's top ranks, which if the deals close would collapse from five major companies to a big three.

The biggest companies are seeking more cost efficiency and scale as the health-care landscape changes because of the Affordable Care Act and other factors. Of the current major health insurers, only UnitedHealth Group Inc., the largest by revenue, is sitting out the merger wave, at least so far.

Under the deal's terms, Indianapolis-based Anthem agreed to pay $188 a share for Cigna, of Bloomfield, Conn., based on Anthem's closing price on May 28. That was the day before the Journal reported that Humana was for sale, a signal to investors that a long-expected consolidation wave in the industry had begun. Using Thursday's closing share price for Anthem, the deal would be valued at $183.36 a share. Cigna shareholders would receive $103.40 in cash and 0.5152 Anthem shares for each share held.

The combination requires approval from federal and state regulators, and legal experts have said antitrust officials are likely to tak e a close look at the huge tandem health-insurance deals. Anthem and Cigna said Friday they believe their deal can pass muster with regulators, and that the combination will benefit consumers by improving affordability and offering a broad range of products and services. They said they are aiming to close the deal in the second half of 2016.

"We have very complementary strengths," said Joseph Swedish, Anthem's chief executive, in an interview. Cigna's chief executive, David Cordani, said the companies' strongest markets are generally not in the same places, and "the geographic overlap is not as redundant as people might think."

In a sign that investors have doubts that the deal--and the parallel tie-up between Aetna and Humana--will be completed, Cigna shares were trading at a 19% discount to the current value of the Anthem offer late Friday morning. Humana, meanwhile, was trading at a 16% discount to the Aetna offer. In late-morning trading, Cigna shares fell 6.4% to $144.45, while Anthem dropped 2.4% to $151.45.

Anthem estimates that the deal will increase its per-share earnings by nearly 10% in the first year after closing, with accretion more than doubling by the second year. Anthem also said the Cigna deal could generate nearly $2 billion in annual synergies, which generally refer to cost savings from eliminating overlap.

Anthem shareholders would own 67% of the combined company, while Cigna shareholders would hold 33%. Based on closing prices Thursday, Cigna had a market value of about $39.7 billion, while Anthem was at $41.1 billion. The companies have each agreed to pay the other a termination fee that equates to $1.8 billion, should the deal fall apart under various circumstances, according to an Anthem spokeswoman.

The agreement between Anthem and Cigna caps off a monthslong, sometimes contentious back-and-forth between the companies, with Anthem at one point going public with its offer.

The two health insurers began holding talks about a combination last summer, but the talks broke down over issues such as who would run a combined company. A point of contention was the role Mr. Cordani would play, including if and when he would run it. In June, Cigna rejected a $47.5 billion offer from Anthem, valued at $184 a share, calling it "inadequate and not in the best interests of Cigna's shareholders."

Friday, the companies said Anthem's Mr. Swedish would be CEO and chairman of the combined company, while Mr. Cordani will become president and operations chief. The two CEOs played up their expected collaboration, detailing the split in their duties and trading compliments. The companies' website dedicated to the deal features a photo of them amicably shaking hands. Two years after the deal closes, Mr. Swedish is expected to relinquish the CEO title. At that time, he said in an interview, Anthem's board will have the freedom to decide the company's chief executive -- implying there is no firm commitment in place that Mr. Cordani will assume the role at that time.

Anthem's board will be expanded to 14 members, the companies said. Mr. Cordani and four independent members of Cigna's board will join Anthem's nine directors.

Mr. Cordani said Cigna, which had raised concerns about regulatory and other issues potentially hindering a deal, had come to believe the challenges were "wholly manageable."

Anthem, which is a Blue Cross and Blue Shield plan provider in 14 states, has a commanding presence particularly in individual and small-employer plans. But it is also a major player in serving large, multistate employers, which it does in partnership with other Blue-plan companies around the country. Cigna, too, is known for its focus on administering coverage for large employers, as well as a burgeoning overseas presence.

Another possible challenge: As a licensee of the Blue Cross Blue Shield Association, Anthem must adhere to certain rules to use the Blue brand. According to Anthem's annual report filed with the Securities and Exchange Commission, the requirements include that two-thirds of a licensee's national net revenue from health plans and related services must stem from Blue-branded business.

Friday, Mr. Swedish said he wanted to emphasize that "we are a Blue organization." He said the Blue requirements wouldn't preclude the Cigna deal from closing, and he expected a collaborative process with the other Blue-plan companies. "I'm optimistic we will meet the test and be in full compliance with the rules," he said in the interview.

An Anthem spokeswoman said the company has many possible ways it could adhere to the Blue rules.

Earlier, Anthem had said that in addition to transitioning Cigna's business in locations where it holds the Blue rights, it could work to plug Cigna's national-employer clients that are based outside its states into the network of Blue plans, which cooperate using a system known as BlueCard.

The Cigna deal, together with the Aetna-Humana announcement, will present federal and state regulators with a particularly complex situation, and experts say they expect the two proposed combinations, likely along with a third, smaller deal announced earlier this month, to be reviewed together.

Analysts at Goldman Sachs Group Inc. looked at the coverage market for big, multistate employers and concluded that antitrust regulators might potentially consider it already on the borderline of concentrated, even before a merger of Cigna and Anthem. But the analysts saw little or no risk of potential divestiture for an Anthem-Cigna combination in the Medicare Advantage, individual or small-group business.

UBS Group AG was Anthem's lead financial adviser. Credit Suisse Group AG also served as a financial adviser to Anthem. Its legal adviser is White & Case LLP. Cigna was advised by Morgan Stanley and Cravath, Swaine & Moore LLP.

Separately, Cigna on Friday raised its profit outlook for the year after reporting strong preliminary results for its second quarter, citing customer growth and medical-cost management.

For the year, Cigna said it is now expecting per-share income from operations of $8.30 a share to $8.60 a share, up from its already-raised forecast of $8.15 to $8.50 a share.

For the second quarter ended in June, Cigna said it expects its profit to be at least $574 million, or $2.21 a share, up from $573 million, or $2.12 a share, a year earlier. Excluding a per-share redemption charge of 25 cents, earnings would easily top the $2.25 a share in earnings analysts polled by Thomson Reuters had forecast.

Revenue is expected to grow 9% to $9.5 billion, while analysts had forecast $9.53 billion in revenue.

Anthem, meanwhile, also raised its 2015 per-share earnings estimate to more than $10, up from $9.90. For the second quarter, Anthem sees per-share earnings of $3.13, or $3.10 excluding certain items. Analysts were expecting per-share earnings of $2.70 in the second quarter and $10.08 for the year.

Dana Mattioli and Chelsey Dulaney contributed to this article

Write to Anna Wilde Mathews at anna.mathews@wsj.com and Liz Hoffman at liz.hoffman@wsj.com

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